Sample records for adjuvant photodynamic therapy

  1. Adjuvant Intraoperative Photodynamic Therapy in Head and Neck Cancer

    PubMed Central

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

    2015-01-01

    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

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    1997-01-01

    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

  4. Combating melanoma: the use of photodynamic therapy as a novel, adjuvant therapeutic tool.

    PubMed

    Davids, L M; Kleemann, B

    2011-10-01

    Metastatic malignant melanoma remains one of the most dreaded skin cancers worldwide. Numerous factors contribute to its resistance to hosts of treatment regimes and despite significant scientific advances over the last decade in the field of chemotherapeutics and melanocytic targets, there still remains the need for improved therapeutic modalities. Photodynamic therapy, a minimally invasive therapeutic modality has been shown to be effective in a number of oncologic and non-oncologic conditions. Using second-generation stable, lipophilic photosensitizers with optimised wavelengths, PDT may be a promising tool for adjuvant therapy in combating melanoma. Potential targets for PDT in melanoma eradication include cell proliferation inhibition, activation of cell death and reduction in pro-survival autophagy and a decrease in the cellular melanocytic antioxidant system. This review highlights the current knowledge with respect to these characteristics and suggests that PDT be considered as a good candidate for adjuvant treatment in post-resected malignant metastatic melanoma. Furthermore, it suggests that primary consideration must be given to organelle-specific destruction in melanoma specifically targeting the melanosomes - the one organelle that is specific to cells of the melanocytic lineage that houses the toxic compound, melanin. We believe that using this combined knowledge may eventually lead to an effective therapeutic tool to combat this highly intractable disease. PMID:21168280

  5. Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors.

    PubMed

    Korbelik, Mladen; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M; Bielawska, Alicja; Separovic, Duska

    2013-09-01

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3-fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction. PMID:23911762

  6. CpG oligodeoxynucleotide as immune adjuvant enhances photodynamic therapy response in murine metastatic breast cancer.

    PubMed

    Xia, Yumin; Gupta, Gaurav K; Castano, Ana P; Mroz, Pawel; Avci, Pinar; Hamblin, Michael R

    2014-11-01

    Breast cancer is the most common cause of cancer death in women. The side effects and complications following current breast cancer therapy can be devastating. Moreover, the prognosis in late stages of the diseases is usually poor. Photodynamic therapy (PDT) is a promising cancer treatment modality that is capable of both local tumor destruction and immune stimulation. However, treatment with PDT alone is often non-curative due to tumor-induced immune cell dysfunction and immune suppression. This phenomenon has motivated a new approach by combining immunostimulants with PDT to enhance anti-tumor immunity. In the present study, we investigated PDT mediated by verteporfin and 690 nm light delivered 15 min later, in combination with an immunomodulation approach using CpG oligodeoxynucleotide for the treatment of 4T1 metastatic breast cancer in a BALB/c immunocompetent mouse model. In vitro, CpG primed immature dendritic cells (DC) via toll like receptor 9 to phagocytose PDT killed tumor cells leading to DC maturation and activation. Peritumoral injection of CpG after PDT in mice gave improved local tumor control and a survival advantage compared to either treatment alone (p < 0.05). CpG may be a valuable dendritic cell targeted immunoadjuvant to combine with PDT. PMID:23922221

  7. Photodynamic therapy with fullerenes†

    PubMed Central

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

    2010-01-01

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

  8. Photodynamic Therapy (PDT): PDT Mechanisms

    PubMed Central

    Allison, Ron R.

    2013-01-01

    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

  9. Photodynamic therapy for unresectable cholangiocarcinoma.

    PubMed

    Tomizawa, Yutaka; Tian, Jianmin

    2012-02-01

    Cholangiocarcinoma (CC) is a rare primary malignancy of the biliary tract with a dismal prognosis. Curative resection can only be applied to a small proportion of early diagnosed patients. Palliative biliary drainage by either percutaneous or endoscopic insertion of endoprostheses improves quality-of-life by reducing pruritis, cholangitis, and pain, but has been reported to improve survival time only slightly. Photodynamic therapy (PDT) is a relatively new local, minimally invasive palliative strategy for unresectable CC. PDT uses a photosensitive molecule that accumulates in proliferating tissue such as tumors. Activation of the photosensitizer by use of light of a specific wavelength generates reactive oxygen species leading to selective tumor-cell death. After initial feasibility studies and promising prospective phase II studies, results from two prospective randomized controlled trials comparing PDT after endoprostheses insertion with endoprostheses alone for patients with unresectable CC have been published. One study resulted in dramatically prolonged median survival in the PDT group (493 days) compared with the non-PDT group (98 days) (P < 0.0001), and significantly improved performance status (PS) in the PDT group. A second study with high baseline patients' PS confirmed the benefit of PDT for survival (630 days in the PDT group compared with 210 days for endoprostheses alone, P < 0.01). The procedures were generally well tolerated. PDT has also been reported to have a favorable outcome as adjuvant and neoadjuvant therapy for CC. Although accumulated data and local expertise are limited, PDT can be regarded as a standard palliative therapy for unresectable CC. PMID:22057285

  10. Photodynamic therapy for epilepsy

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

    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.

  11. 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

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

    2011-01-01

    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

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

    E-print Network

    2004-01-01

    Photodiagnosis and Photodynamic Therapy (2004) 1, 157--171 REVIEW Photodynamic therapy for chest Available online 13 September 2004 KEYWORDS Photodynamic therapy; Chest wall recurrence; Breast cancer; LED with chest wall re-recurrence from breast cancer. © 2004 Elsevier B.V. All rights reserved. Contents

  13. Veterinary photodynamic therapy: a review.

    PubMed

    Buchholz, Julia; Walt, Heinrich

    2013-12-01

    Whereas in human medicine photodynamic therapy represents a well-known and recognized treatment option for diverse indications, it is still little known and unfortunately not yet established treatment option for pets. Various photosensitizers and light sources have been used and clinical results have been published. The main indication is a frequently occurring skin tumor in cats: in situ carcinoma/squamous cell carcinoma, mainly found in not or only slightly pigmented areas of the head. For early stages of this tumor, promising results have been published, partly using new, selective drugs to decrease light sensitivity after systemic administration and to increase response rates. Other possible indications are urinary tract neoplasia of dogs and equine sarcoids, the latter representing very common tumors in horses where no effective treatment is known so far. This review article summarizes the role of photodynamic therapy in veterinary medicine. PMID:24284083

  14. Photodynamic therapy of recurrent cerebral glioma

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

    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.

  15. Photodynamic Therapy and Inflammatory Disorders

    Microsoft Academic Search

    Cara Garretson; Amy Forman Taub

    \\u000a While still in its infancy, photodynamic therapy is becoming a prominent treatment option in a number of dermatological diseases,\\u000a such as psoriasis, lichen planus, lichen sclerosis, morphea\\/scleroderma, vitiligo, necrobiosis, lipoidica diabeticorum, sarcoidosis,\\u000a granuloma annulare, alopecia areata, and Darier’s disease. Given the breadth of clinical implications, it is clear that both\\u000a basic science and clinical studies are still needed to learn

  16. Image-Guided Photodynamic Cancer Therapy

    Microsoft Academic Search

    Zheng-Rong Lu; Anagha Vaidya

    Photodynamic therapy is a therapeutic modality with a long history. It has been historically known in ancient India and China\\u000a for the treatment of skin disorders. In Western medicine, the first experimental evidence of photodynamic therapy was reported\\u000a by Raab et al. who observed the lethality of acridine dyes to paramecium in the presence of light [1]. The photodynamic effect

  17. [Antimicrobial photodynamic therapy: current view].

    PubMed

    Pal'chun, V T; Lapchenko, A S; Lapchenko, A A; Gurov, A V; Kucherov, A G

    2007-01-01

    Growing resistance of bacteria to wide-spectrum antibiotics gave rise to a search for new approaches to antimicrobial therapy. Photodynamic therapy (PT) was proposed for fighting against infections. It combines effects of a photosensitiser and visible light. PT produces reactive oxygen species able to kill cells. High response to PT was achieved in the treatment of local infections, in particular, in the treatment of pyoinflammatory ENT diseases caused both by gram-positive and gram-negative bacteria, fungi, especially diseases caused by bacteria with antibiotic polyresistance. PMID:17690648

  18. Photodynamic therapy in endodontics: a literature review.

    PubMed

    Trindade, Alessandra Cesar; De Figueiredo, José Antônio Poli; Steier, Liviu; Weber, João Batista Blessmann

    2015-03-01

    Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics. PMID:25719896

  19. Treatment of rheumatoid arthritis using photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

    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.

  20. Photodynamic Diagnosis and Therapy of Cancer

    SciTech Connect

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

    2010-01-05

    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.

  1. Antimicrobial photodynamic therapy: An overview

    PubMed Central

    Rajesh, S.; Koshi, Elizabeth; Philip, Koshi; Mohan, Aparna

    2011-01-01

    Inflammatory periodontal disease caused by dental plaque is characterized by the clinical signs of inflammation and loss of periodontal tissue support. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. But the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. The possibility of development of resistance to antibiotics by the target organism has led to the development of a new antimicrobial concept with fewer complications. Photodynamic therapy (PDT) involves the use of low power lasers with appropriate wavelength to kill micro organisms treated with a photosensitizer drug. PDT could be a useful adjunct to mechanical as well as antibiotics in eliminating periopathogenic bacteria. PMID:22368354

  2. Immunological effects of photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1990-07-01

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

  3. Photodynamic therapy of acne vulgaris.

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

  4. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

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

    1993-05-01

    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.

  5. Photodynamic therapy for esophageal cancer.

    PubMed

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

    2014-03-01

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

  6. Photodynamic therapy of gastrointestinal cancers

    NASA Astrophysics Data System (ADS)

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

    1994-03-01

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

  7. Photodynamic therapy for esophageal cancer

    PubMed Central

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

    2014-01-01

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

  8. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    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

  9. Photodynamic therapy of gastric cancer

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

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

  10. Functionalized fullerenes in photodynamic therapy.

    PubMed

    Huang, Ying-Ying; Sharma, Sulbha K; Yin, Rui; Agrawal, Tanupriya; Chiang, Long Y; Hamblin, Michael R

    2014-09-01

    Since the discovery of C60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine CO60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C60, C70 and C84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT. PMID:25544837

  11. Photodynamic therapy for skin cancer

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

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

  12. Porphyrins for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Pascu, Mihail-Lucian

    2001-06-01

    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.

  13. Photodynamic therapy of diseased bone

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.

  14. Antimicrobial Photodynamic Inactivation and Photodynamic Therapy for Infections

    PubMed Central

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

    2010-01-01

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

  15. Photodynamic therapy in neurosurgery: a review

    Microsoft Academic Search

    Herwig Kostron; Alois Obwegeser; Rosanna Jakober

    1996-01-01

    Photodynamic therapy (PDT) has been investigated extensively, both experimentally and clinically, as an adjunctive treatment in the neuro-oncological field. It is based on the more selective accumulation of a photosensitizer in malignant than normal tissue with low systemic toxicity. Subsequent light activation induces photo-oxidation, followed by selective tumour destruction via vascular and direct cellular mechanisms. Malignant brain tumours carry a

  16. Flexible textile light diffuser for photodynamic therapy

    Microsoft Academic Search

    Barbel Selm; Martin Camenzind

    2005-01-01

    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

  17. Photodynamic therapy of advanced malignant tumors

    Microsoft Academic Search

    Lian-Xing Wang; Lu-Pin Dai; Wen-Qin Lu

    1993-01-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with

  18. Interstitial photodynamic laser therapy in interventional oncology

    Microsoft Academic Search

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

    2004-01-01

    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

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

    Microsoft Academic Search

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

    2007-01-01

    Ocular photodynamic therapy (PDT) was introduced as a novel treatment for neovascular forms of age-related macular degeneration and choroidal neovascularization (CNV) secondary to pathologic myopia in the mid\\/end 1990s. The current treatment recommendations are based on the results of two large, prospective, multicenter, randomized clinical trials (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Studies)

  20. Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization

    Microsoft Academic Search

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

    2001-01-01

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

  1. Interstitial Photodynamic Therapy of Brain Tumors

    Microsoft Academic Search

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

    2010-01-01

    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

  2. Photodynamic therapy for polypoidal choroidal vasculopathy.

    PubMed

    Nowak-Sliwinska, Patrycja; van den Bergh, Hubert; Sickenberg, Michel; Koh, Adrian H C

    2013-11-01

    The first effective therapy for exudative macular degeneration (AMD) was Photodynamic Therapy (PDT). Diagnosis of the disease was to a large extent by fluorescein angiography (FA). Distinguishing between the leaky choroidal neovessels (CNV) associated with exudative AMD, and the polypoidal structures associated with Polypoidal Choroidal Vasculopathy (PCV) is not always easy using FA alone. The switch to Indocyanine Green angiography helped to pinpoint PCV, and thus to study the efficacy of photodynamic therapy of this particular form of retinal disease, which is more frequently encountered among pigmented individuals. The results appear to be quite promising, and in the year following treatment only a small fraction of the patients had to be retreated. Alternatively, treating PCV with repeated intravitreal VEGF blocking agents was not as successful as it was in the treatment of wet AMD. However, combining PDT-induced angio-occlusion of the polypoidal lesions with anti-vascular endothelial growth factor therapy was shown to be quite effective, and the combination of PDT with an anti-angiogenic agent as well as a steroid, in a triple therapy, was recently also shown to be a quite promising option. In the present article we review the data on PDT of PCV, including combination therapies and alternative treatments. We also report on similarities and differences between AMD and PCV. PMID:24140257

  3. Photodynamic therapy of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  4. Photoangioplasty: new applications of photodynamic therapy in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Rockson, Stanley G.

    2000-05-01

    Atherosclerosis has traditionally held appeal as a pathologic entity in which photodynamic therapy might arrest or reverse the manifestations of disease. Earlier attempts to bring photodynamic therapy to the human clinical arena were hampered by the limitations of the photosensitizers under investigation, including the propensity to phototoxic manifestations and light-induced trauma to surrounding, normal vascular tissues. Many of these inherent limitations may be circumvented by newer photosensitizers that are activated at longer, more optimal wavelengths of light energy. Advances in fiberoptic catheter design for the endovascular delivery of light have also contributed to the greater applicability of photodynamic therapy to human atherosclerosis. Initial experiences with one family of photosensitizers, the texaphyrins, indicate that photodynamic therapy of human peripheral arterial atherosclerosis is feasible, safe, and well-tolerated. Photodynamic therapy of atherosclerosis holds promise for the treatment of de novo atherosclerosis and may have future applicability in the treatment, and perhaps prevention, of restenosis.

  5. Cell Death Pathways in Photodynamic Therapy of Cancer

    E-print Network

    Mroz, Pawel

    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 ...

  6. Photodynamic therapy for treatment subretinal neovascularization

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

  7. [New trends and safety of photodynamic therapy].

    PubMed

    Osma?ek, Tomasz; Go?li?ski, Tomasz; Mielcarek, Jadwiga; Osma?ek, Edyta

    2012-01-01

    Photodynamic therapy (PDT) is used mainly in tumor diagnosis and treatment. It is obvious that PDT can increase the efficiency of traditional methods such as surgery, chemotherapy or radiotherapy. Unfortunately, photosensitizers used in the treatment are still imperfect. According to severe side effects, patients need to change their life habits even for several weeks. The problem is attributed to insufficient selectivity of dyes toward cancer tissues. Safety of PDT can be improved by application of various carriers including liposomes, nanotubes or nanoparticles. Binding of photosensitizers to tumor specific molecules opens broad new possibilities for PDT. PMID:23646448

  8. Photodynamic therapy using glycol chitosan grafted fullerenes.

    PubMed

    Kwag, Dong Sup; Oh, Nam Muk; Oh, Young Taik; Oh, Kyung Taek; Youn, Yu Seok; Lee, Eun Seong

    2012-07-15

    Glycol chitosan (GC)-grafted fullerene (GC-g-C(60)) conjugates were developed for use in photodynamic therapy of tumor cells. GC-g-C(60) was synthesized in anhydrous benzene/dimethylsulfoxide (DMSO) co-solvent via the chemical conjugation of free amine groups of GC to CC double bonds of C(60). The GC-g-C(60) with 5×10(-4) C(60) molecules per one repeating unit of GC was soluble in water. As C(60) molecules conjugated to GC increased to 0.16 molecules per one repeating unit of GC, GC-g-C(60) started to form supramolecular assemblies (?30 nm) stabilized in phosphate buffer saline (PBS, 150 mM, pH 7.4). Upon 670 nm light illumination, photo-responsive properties of GC-g-C(60) allowed tremendous singlet oxygen generation in tumor cells for super phototoxicity. GC-g-C(60) also showed highly increased tumor accumulation ability for in vivo tumor of KB tumor-bearing nude mice. It is expected that our GC-g-C(60) conjugate may be a good candidate for in vivo photodynamic therapy in various malignant tumor cells. PMID:22537808

  9. Singlet oxygen dosimetry modeling for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Liang, Xing; Wang, Ken Kang-hsin; Zhu, Timothy C.

    2012-02-01

    Photodynamic therapy (PDT) is an important treatment modality for cancer and other localized diseases. In addition to PDT dose, singlet oxygen (1O2) concentration is used as an explicit PDT dosimetry quantity, because 1O2 is the major cytotoxic agent in photodynamic therapy, and the reaction between 1O2 and tumor tissues/cells determines the treatment efficacy. 1O2 concentration can be obtained by the PDT model, which includes diffusion equation for the light transport in tissue and macroscopic kinetic equations for the generation of the singlet oxygen. This model was implemented using finite-element method (FEM) by COMSOL. In the kinetic equations, 5 photo-physiological parameters were determined explicitly to predict the generation of 1O2. The singlet oxygen concentration profile was calculated iteratively by comparing the model with the measurements based on mice experiments, to obtain the apparent reacted 1O2concentration as an explicit PDT dosimetry quantity. Two photosensitizers including Photofrin and BPD Verteporfin, were tested using this model to determine their photo-physiological parameters and the reacted 1O2 concentrations.

  10. Photodynamic therapy of intraductal papillary mucinous neoplasm.

    PubMed

    Topazian, M; Zhong, N; Baron, T H; Vege, S S; Wang, K K

    2012-02-01

    Intraductal papillary mucinous neoplasm (IPMN) of the main pancreatic duct is usually treated by surgical excision of the affected pancreas. Nonoperative ablative therapies have not been described. We treated IPMN of the pancreatic duct with photodynamic therapy (PDT) in a patient who was a poor operative candidate. Porfimer sodium was administered intravenously, and laser light was delivered by a diffusing catheter placed in the pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP). Imaging and biopsy findings of IPMN resolved after PDT, and symptoms also resolved. Metastatic cancer was diagnosed 2 years after PDT had been initiated. Pancreatic PDT was well tolerated in this case, and may be a therapeutic option for selected patients with IPMN of the main pancreatic duct. PMID:22271032

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  12. Photonic metallic nanostructures in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Fierascu, R. C.; Dumitriu, Irina

    2009-01-01

    Plasmons are resonant modes that involve the interaction between free charges and light. Nanoparticle-based photonic explorers have been developed for photodynamic therapy (PDT). PDT has been widely used in both oncological (e.g., tumors) and nononcological (e.g., age-related macular degeneration, localized infection, and nonmalignant skin conditions) applications. Three primary components are involved in PDT: light, a photosensitizing drug, and oxygen. The photosensitizer adsorbs light energy, which it then transfers to molecular oxygen to create an activated form of oxygen called singlet oxygen. The singlet oxygen is a cytotoxic agent and reacts rapidly with cellular components to cause damage that ultimately leads to cell death and tumor destruction. The changed topography of the film surface after deposition is caused by a local material transport and a material separation between formed particles (probably AgNO3) and an embedding polymer matrix as chitosan. This paper focuses on the current use of injectable in situ Au/(Ag)/chitosan hydrogels in cancer photodynamic treatment. Formulation protocols for their cytotoxic properties, their effect on cell growth in vitro and inhibition of tumor growth in vivo using mouse models, are discussed.

  13. Photodynamic Cancer Therapy—Recent Advances

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2011-09-01

    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.

  14. Photodynamic therapy of cerebral glioma--a review Part I--a biological basis.

    PubMed

    Stylli, Stanley S; Kaye, Andrew H

    2006-07-01

    Photodynamic therapy (PDT) has been investigated extensively in the laboratory for decades, and for over 25 years in the clinical environment, establishing it as a useful adjuvant to standard treatments for many cancers. A combination of both photochemical and photobiological processes occur that lead to the eventual selective destruction of the tumour cells. It is a potentially valuable adjuvant therapy that can be used in conjunction with other conventional therapies for the treatment of cerebral glioma. PDT has undergone extensive laboratory studies and clinical trials with a variety of photosensitizers (PS) and tumour models of cerebral glioma. Many environmental and genetically based factors influence the outcome of the PDT response. The biological basis of PDT is discussed with reference to laboratory and preclinical studies. PMID:16554159

  15. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    PubMed Central

    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

    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

  16. Dosimetry for photodynamic therapy of endometrial tissue

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

    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.

  17. The role of photodynamic therapy (PDT) physics

    PubMed Central

    Zhu, Timothy C.; Finlay, Jarod C.

    2008-01-01

    Photodynamic therapy (PDT) is an emerging treatment modality that employs the photochemical interaction of three components: light, photosensitizer, and oxygen. Tremendous progress has been made in the last 2 decades in new technical development of all components as well as understanding of the biophysical mechanism of PDT. The authors will review the current state of art in PDT research, with an emphasis in PDT physics. They foresee a merge of current separate areas of research in light production and delivery, PDT dosimetry, multimodality imaging, new photosensitizer development, and PDT biology into interdisciplinary combination of two to three areas. Ultimately, they strongly believe that all these categories of research will be linked to develop an integrated model for real-time dosimetry and treatment planning based on biological response. PMID:18697538

  18. Photodynamic therapy: superficial and interstitial illumination

    NASA Astrophysics Data System (ADS)

    Svanberg, Katarina; Bendsoe, Niels; Axelsson, Johan; Andersson-Engels, Stefan; Svanberg, Sune

    2010-07-01

    Photodynamic therapy (PDT) is reviewed using the treatment of skin tumors as an example of superficial lesions and prostate cancer as an example of deep-lying lesions requiring interstitial intervention. These two applications are among the most commonly studied in oncological PDT, and illustrate well the different challenges facing the two modalities of PDT-superficial and interstitial. They thus serve as good examples to illustrate the entire field of PDT in oncology. PDT is discussed based on the Lund University group's over 20 yr of experience in the field. In particular, the interplay between optical diagnostics and dosimetry and the delivery of the therapeutic light dose are highlighted. An interactive multiple-fiber interstitial procedure to deliver the required therapeutic dose based on the assessment of light fluence rate and sensitizer concentration and oxygen level throughout the tumor is presented.

  19. Photodynamic therapy of cancer: an update.

    PubMed

    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

    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 patients with 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

  20. Photodynamic Therapy and Cell Death Pathways

    PubMed Central

    Oleinick, Nancy L.

    2015-01-01

    Photodynamic therapy (PDT) is the term used to describe the irradiation of photosensitized cells or tissue with phototoxic consequences. This process can result in the rapid initiation of not only apoptosis, an irreversible death pathway, but also autophagy. The procedures described here are designed to characterize the correlation between the PDT dose vs. survival of cells in vitro, the apoptotic effects of photodamage, and the extent of an autophagic response. These are assessed by clonogenic assays, observation of condensed chromatin characteristic of apoptosis, activation of “executioner” caspases, and the autophagic flux as indicated by comparing accumulation of the LC3-II protein under conditions where processing of autophagosomes is retarded vs. is not retarded. PMID:20552338

  1. Feasibility of chemiluminescence as photodynamic therapy dosimetor

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

  2. Reflectance and fluorescence spectroscopies in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Finlay, Jarod C.

    In vivo fluorescence spectroscopy during photodynamic therapy (PDT) has the potential to provide information on the distribution and degradation of sensitizers, the formation of fluorescent photoproducts and changes in tissue autofluorescence induced by photodynamic treatment. Reflectance spectroscopy allows quantification of light absorption and scattering in tissue. We present the results of several related studies of fluorescence and reflectance spectroscopy and their applications to photodynamic dosimetry. First, we develop and test an empirical method for the correction of the distortions imposed on fluorescence spectra by absorption and scattering in turbid media. We characterize the irradiance dependence of the in vivo photobleaching of three sensitizers, protoporphyrin IX (PpIX), Photofrin and mTHPC, in a rat skin model. The photobleaching and photoproduct formation of PpIX exhibit irradiance dependence consistent with singlet oxygen (1O2)-mediated bleaching. The bleaching of mTHPC occurs in two phases, only one of which is consistent with a 1O 2-mediated mechanism. Photofrin's bleaching is independent of irradiance, although its photoproduct formation is not. This can be explained by a mixed-mechanism bleaching model. Second, we develop an algorithm for the determination of tissue optical properties using diffuse reflectance spectra measured at a single source-detector separation and demonstrate the recovery of the hemoglobin oxygen dissociation curve from tissue-simulating phantoms containing human erythrocytes. This method is then used to investigate the heterogeneity of oxygenation response in murine tumors induced by carbogen inhalation. We find that while the response varies among animals and within each tumor, the majority of tumors exhibit an increase in blood oxygenation during carbogen breathing. We present a forward-adjoint model of fluorescence propagation that uses the optical property information acquired from reflectance spectroscopy to obtain the undistorted fluorescence spectrum over a wide range of optical properties. Finally, we investigate the ability of the forward-adjoint theory to extract undistorted fluorescence and optical property information simultaneously from a single measured fluorescence spectrum. This method can recover the hemoglobin oxygen dissociation curve in tissue-simulating phantoms with an accuracy comparable to that of reflectance-based methods while correcting distortions in the fluorescence over a wide range of absorption and scattering coefficients.

  3. Progress of Photodynamic Therapy in Gastric Cancer

    PubMed Central

    Narahara, Hiroyuki; Otani, Toru; Okuda, Shigeru

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm2 for an argon dye laser and 60 J/cm2 for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm2 in area to 4 cm in diameter, i.e. 13 cm2 by employing a new excimer dye laser model, which could emit 4mJ/pulse with 80 Hz pulse frequency. (4) The depth of cancer invasion which could be treated by PDT was increased from about 4 mm, i.e. the superficial part of the submucosal layer (SM-1) to more than 10 mm in depth, i.e. the proper muscular layer. These improvements owe much to the pulse laser, the photodynamic action induced by which permits deeper penetration than that of a continuous wave laser. (5) We employed a side-viewing fiberscope for gastric PDT to irradiate the lesion from an angle of 90°. (6) We designed a simple cut quartz fiber for photoradiation with a spiral spring thickened toward the end. (7) We developed an endoscopic device for photoradiation in PDT which achieves accurate and efficient irradiation. As a result of these improvements a higher cure rate was obtained even with a lower light dose of irradiation. PMID:18493500

  4. Colonic mucosectomy using laser photodynamic therapy

    SciTech Connect

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

    1989-06-01

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

  5. EARLY CLINICAL EXPERIENCE WITH 5-AMINOLEVULINIC ACID FOR THE PHOTODYNAMIC THERAPY OF UPPER TRACT UROTHELIAL TUMORS

    Microsoft Academic Search

    Raphaela Waidelich; Alfons Hofstetter; Herbert Stepp; Reinhold Baumgartner; Ernst Weninger; Martin Kriegmair

    1998-01-01

    PurposePhotodynamic therapy is effective in the treatment of superficial urothelial cancer of the bladder. We report our experience with photodynamic therapy for the treatment of upper urinary tract transitional cell carcinoma.

  6. Photodynamic Therapy for Head and Neck Cancer

    PubMed Central

    Kato, Harubumi; Okunaka, Tetsuya; Saeki, Tetsuo; Ohashi, Shinya; Okudaira, Tadao; Lee, A. Masaji; Yoshida, Hikari; Maruoka, Hidehiro; Ito, Hiroyuki; Funasaka, Sotaro

    1996-01-01

    Photodynamic therapy (PDT) is a recently developed treatment involving the use of a photosensitizer and low power light, usually from a laser, to selectively destroy tumor cells. At present, we perform PDT for head and neck cancer using argon or excimer dye lasers with hematoporphyrin derivative as a photosensitizer. This study attempted to assess the utility and safety of PDT and to investigate the long-term outcome. All 24 patients had squamous cell carcinoma: 15 with laryngeal, 5 with lingual or oral, and 4 with pharyngeal cancer and were treated by PDT. Data were obtained from records from February 1988 through April 1995. After PDT, 12 of 15 laryngeal cancer patients were classified as having a complete remission (CR), as were 2 of the 5 lingual or oral and one of the 4 pharyngeal cancer patients. The patients were followed for 8 to 153 months. The longest duration of CR in patients treated by PDT alone was 148 months. Photosensitivity was experienced by all patients, but required no treatment. Liver, kidneys, and bone marrow showed no abnormal values. There were no clinically relevant adverse reactions, and patients with severe complications due to other types of treatment and elderly patients were also treated safely with this therapy. PMID:18493416

  7. Photodynamic Therapy for Infections: Clinical Applications

    PubMed Central

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

    2012-01-01

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

  8. Tissue temperature monitoring during interstitial photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  9. Photodynamic therapy (PDT) as a biological modifier

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

    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) ).

  10. Light delivery schemes for uterine photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1994-03-01

    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.

  11. Photodynamic therapy of breast cancer with photosense

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

    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.

  12. Progress in photodynamic therapy on tumors

    NASA Astrophysics Data System (ADS)

    Tian, Y. Y.; Wang, L. L.; Wang, W.

    2008-10-01

    Photodynamic therapy (PDT) is a promising treatment on neoplastic pathologic tissues, which involves the administration of a photosensitizing agent followed by the exposure of the tissue to visible nonthermal light. Light energy is captured and transferred to other molecules resulting in the formation of short-lived energetic species, which interact with biological systems and then produce tissue damage. Photosensitizer can be taken up selectively by tumor cells because of the upregulation of low-density lipoprotein receptor-mediated endocytosis and the acidic tumor environments. In recent years, the application of PDT in the treatment of malignant lesions has increased dramatically. The first health agency approval for PDT was granted for Photofrin in Canada in 1993, and, now, it is licensed in many countries for the treatment of cancers. Although Photofrin is the most commonly used photosensitizer, it has significant side effects. Therefore, major effort has been invested in the development of new sensitizers and, to this end, many photosensitizers have been described and some are now in clinical trials.

  13. Photodynamic therapy (PDT) for lung cancer

    NASA Astrophysics Data System (ADS)

    Moghissi, K.; Dixon, Kate

    2005-11-01

    The Yorkshire Laser Centre has been engaged in Photodynamic Therapy (PDT) since 1990. In this article we present our experience highlighting the lesson learnt. 280 bronchoscopic PDT treatments have been carried out in 160 patients divided in 2 groups. Group A: (Nr 144) with advanced inoperable disease and Group E (Nr 16) with early stage cancer. PDT method was intravenous administration of 2mg/kg bw of Photofrin followed by bronchoscopic illumination of 630nm laser light. There was no procedure-related mortality. A total of 9 cases of photosensitivity (skin burn) occurred in the series (5.6% of patients). Every patient in both groups expressed their total satisfaction to treatment. Group A: Symptom relief was achieved in all. This was matched by improvement in significant bronchial opening (58.1%). Survival was 9.6 months (mean).This was greater in patients with better performance status and lower stage of disease. Group E: Every patient had a complete response to treatment. Survival in this group was 75.4 months (mean). We conclude that bronchoscopic PDT is indicated in both advanced and early stage lung cancer. In the former it provides symptomatic relief in all and survival benefit in some; in the latter it achieves long survival and potential cure.

  14. Pecularities of clinical photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

    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.

  15. Integrating spheres for improved skin photodynamic therapy.

    PubMed

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

    2010-01-01

    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

  16. Photodynamic therapy: Biophysical mechanisms and molecular responses

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya

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

  17. Melanoma and IFN alpha: potential adjuvant therapy.

    PubMed

    Bottoni, U; Clerico, R; Paolino, G; Corsetti, P; Ambrifi, M; Brachini, A; Richetta, A; Nisticò, S; Pranteda, G; Calvieri, S

    2014-01-01

    Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness ?2.00 mm presented a significantly longer mean DFS than patients with Breslow ?2.01 mm (p = 0.01). Using non- parametric Spearman?s Coefficient test we found association between DFS and Breslow thickness (p < 0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p < 0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values ? 2.00 mm (p < 0.0001), and absence of ulceration (p <0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma ? 4.01 mm that was not ulcerated; patients with Breslow ? 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits. PMID:25001659

  18. Laser effect in photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

    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.

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

    PubMed

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

    2014-12-18

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

  20. Optical delivery and monitoring of photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

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

    2004-10-01

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

  1. 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)

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

    2009-06-01

    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.

  2. Photodynamic therapy of onychomycosis caused by Trichophyton rubrum.

    PubMed

    Piraccini, Bianca Maria; Rech, Giulia; Tosti, Antonella

    2008-11-01

    A combination of topical and oral antifungals is widely used to treat onychomycosis, but treatment failure is common and oral drugs may cause toxicity and potential drug interactions. For this reason, new approaches and strategies should be considered. The following case shows that photodynamic therapy (PDT) may represent an alternative noninvasive approach to treatment of onychomycosis. PMID:19119130

  3. Photochemical predictive analysis of photodynamic therapy in dermatology

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    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.

  4. Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma.

    PubMed

    Qumseya, Bashar J; David, Waseem; Wolfsen, Herbert C

    2013-01-01

    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

  5. Differential cell photosensitivity in photodynamic therapy of the rat endometrium

    Microsoft Academic Search

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

    1996-01-01

    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

  6. Pretreatment to Enhance Protoporphyrin IX Accumulation in Photodynamic Therapy

    Microsoft Academic Search

    M. J. P. Gerritsen; T. Smits; M. M. Kleinpenning; P. E. J. van Erp

    2009-01-01

    The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an important negative factor in ALA uptake. This review has its focus on pretreatment of the skin in order to

  7. MEASUREMENT OF REACTIVE OXYGEN SPECIES AFTER PHOTODYNAMIC THERAPY IN VITRO

    Microsoft Academic Search

    A b s t r a c t Photodynamic therapy (PDT) is an emerging modality for the treatment of neoplastic and non- neoplastic diseases. It is based on the use of a sensitiser, which is localised in target tissue, light, and molecular oxygen. Sensitisers are activated with the appropriate wavelength of light and then are excited to the long-lived triplet

  8. Optical dosimetry for interstitial photodynamic therapy

    Microsoft Academic Search

    M. R. Arnfield; J. Tulip; M. Chetner; M. S. McPhee

    1989-01-01

    An approach to photodynamic treatment of tumors is the interstitial implantation of fiber optic light sources. Dosimetry is critical in identifying regions of low light intensity in the tumor which may prevent tumor cure. We describe a numerical technique for calculating light distributions within tumors, from multiple fiber optic sources. The method was tested using four translucent plastic needles, which

  9. Photodynamic Therapy in Treatment of Oral Lichen Planus

    PubMed Central

    Mostafa, Diana; Tarakji, Bassel

    2015-01-01

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

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

    Microsoft Academic Search

    Richard F Spaide; John Sorenson; Leandro Maranan

    2003-01-01

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

  11. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide.

    PubMed

    Tian, Bo; Wang, Chao; Zhang, Shuai; Feng, Liangzhu; Liu, Zhuang

    2011-09-27

    Graphene with unique physical and chemical properties has shown various potential applications in biomedicine. In this work, a photosensitizer molecule, Chlorin e6 (Ce6), is loaded on polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular ?-? stacking. The obtained GO-PEG-Ce6 complex shows excellent water solubility and is able to generate cytotoxic singlet oxygen under light excitation for photodynamic therapy (PDT). Owing to the significantly enhanced intracellular trafficking of photosensitizers, our GO-PEG-Ce6 complex offers a remarkably improved cancer cell photodynamic destruction effect compared to free Ce6. More importantly, we show that the photothermal effect of graphene can be utilized to promote the delivery of Ce6 molecules by mild local heating when exposed to a near-infrared laser at a low power density, further enhancing the PDT efficacy against cancer cells. Our work highlights the promise of using graphene for potential multifunctional cancer therapies. PMID:21815655

  12. Towards image-guided photodynamic therapy of Glioblastoma

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    PubMed Central

    Korbelik, M; Cooper, P D

    2006-01-01

    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

  14. Photodynamic therapy for the treatment of buccal candidiasis in rats

    Microsoft Academic Search

    Juliana Campos Junqueira; Joyce da Silva Martins; Raquel Lourdes Faria; Carlos Eduardo Dias Colombo; Antonio Olavo Cardoso Jorge

    2009-01-01

    The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental\\u000a candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated\\u000a with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P?); treated only with photosensitizer (L?-P+);\\u000a not treated with laser or photosensitizer

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

    Microsoft Academic Search

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

    2007-01-01

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

  16. Photophysics and photochemistry of photodynamic therapy: fundamental aspects

    Microsoft Academic Search

    K. Plaetzer; B. Krammer; J. Berlanda; F. Berr; T. Kiesslich

    2009-01-01

    Photodynamic therapy (PDT) is a treatment modality for cancer and various other diseases. The clinical protocol covers the\\u000a illumination of target cells (or tissue), which have been loaded with a photoactive drug (photosensitizer). In this review\\u000a we describe the photophysical and primary photochemical processes that occur during PDT. Interaction of light with tissue\\u000a results in attenuation of the incident light

  17. Treatment of canine oral squamous cell carcinomas with photodynamic therapy

    Microsoft Academic Search

    D L McCaw; E R Pope; J T Payne; R V Tompson; D Tate

    2000-01-01

    Eleven dogs with naturally occurring oral squamous cell carcinomas were treated with photodynamic therapy (PDT) using Photochlor (HPPH) as the photosensitizer. The largest length of the tumours measured in a two-dimensional plane ranged from 0.9 to 6.8 cm. Seven of the tumours invaded underlying bone as determined by radiograph appearance. Photochlor was injected intravenously at a dose of 0.3 mg

  18. Photodynamic therapy of tumours and other diseases using porphyrins

    Microsoft Academic Search

    John D. Spikes; Giulio Jori

    1987-01-01

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

  19. Simultaneous two-photon excitation of photodynamic therapy agents

    SciTech Connect

    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

    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.

  20. Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples

    Microsoft Academic Search

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

    1998-01-01

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

  1. Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization

    Microsoft Academic Search

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

    2002-01-01

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

  2. Photodynamic therapy with verteporfin for retinal angiomatous proliferation

    Microsoft Academic Search

    Francesco Boscia; Maurizio Battaglia Parodi; Claudio Furino; Michele Reibaldi; Carlo Sborgia

    2006-01-01

    Purpose  The aim of this study was to evaluate the results of photodynamic therapy (PDT), using verteporfin, for subfoveal neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) with pigment epithelial detachment (PED) and\\/or choroidal neovascularization (CNV).Methods  In this non-comparative, consecutive, interventional, case series, the data on 21 eyes (19 with stage 2 and two with stage 3 RAP) of 20 patients were

  3. Photodynamic therapy of choroidal hemangioma: two case reports

    Microsoft Academic Search

    Irene Barbazetto; Ursula Schmidt-Erfurth

    2000-01-01

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

  4. Epigenetic remodeling combined with photodynamic therapy elicits anticancer immune responses.

    PubMed

    Wachowska, Malgorzata; Gabrysiak, Magdalena; Golab, Jakub

    2014-01-01

    Photodynamic therapy has been shown to induce strong immunity against tumor cells expressing exogenous tumor-associated antigens (TAAs), including P1A antigen. Cancer cells can evade the immune system by epigenetic silencing of TAAs, while DNA methyltransferase inhibitors, such as 5-aza-2'-deoxycytidine (5-aza-dC) can restore the expression of silenced or downregulated TAA. Thus, epigenetic remodeling with 5-aza-dC combined with PDT can elicit robust and durable antitumor immunity. PMID:25057447

  5. In vitro photodynamic therapy on melanoma cell lines with phthalocyanine

    Microsoft Academic Search

    H. Kolarova; P. Nevrelova; R. Bajgar; D. Jirova; K. Kejlova; M. Strnad

    2007-01-01

    Photodynamic therapy (PDT) is a new treatment modality of tumours. The photochemical interactions of sensitizer, light, and molecular oxygen produce singlet oxygen and other forms of active oxygen, such as peroxide, hydroxyl radical and superoxid anion. Phthalocyanine ClAlPcS2, belonging among the promising second generation of sensitizers, was tested as an inducer of photodamage. We report the production of reactive oxygen

  6. Photodynamic therapy for the treatment of buccal candidiasis in rats.

    PubMed

    Junqueira, Juliana Campos; Martins, Joyce da Silva; Faria, Raquel Lourdes; Colombo, Carlos Eduardo Dias; Jorge, Antonio Olavo Cardoso

    2009-11-01

    The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L-P- group. The group L+P- presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L-P+ group showed tissue lesions similar to those of the L-P- group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups. PMID:19408038

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  8. Tumor Vasculature Targeted Photodynamic Therapy for Enhanced Delivery of Nanoparticles

    PubMed Central

    2015-01-01

    Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors’ origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as “smart” carriers that site-specifically deliver 1O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine. PMID:24806291

  9. Adjuvant hormonal therapy for stage I endometrial cancer

    PubMed Central

    Gien, L.; Kwon, J.; Oliver, T.K.; Fung-Kee-Fung, M.

    2008-01-01

    Question What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? Perspectives There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. Outcomes Reports were sought that included at least one of the following outcomes: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. Methodology The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg). Results Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials. In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%; however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups. The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05; 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10; 95% ci: 0.91 to 1.34). Practice Guideline Target Population This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer. Recommendation The available evidence does not demonstrate any benefit for adjuvant hormonal therapy. The use of hormonal therapy is not recommended as adjuvant treatment for patients with stage i endometrial cancer. PMID:18596890

  10. The effect of laser wavelength in photodynamic therapy and phototherapy for superficial skin diseases

    Microsoft Academic Search

    Farhad H. Mustafa; Mohamad S. Jaafar; Asaad H. Ismail; Hend A. A. Houssein

    2011-01-01

    Due to the low dose absorption in epidermis layer in photodynamic therapy (PDT) and non-ionizing interaction, red laser 635 nm wavelengths radiation proved to be a potential tool for propagating laser in skin. The laser enable sufficient amount of light to penetrate biological tissue and activate the dyes for treatment of superficial skin diseases. Therapy with photodynamic sensitizers and modulation

  11. Optical dosimetry for interstitial photodynamic therapy

    SciTech Connect

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

    1989-07-01

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

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed

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

    2014-01-01

    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

  14. Dramatic regression of presumed acquired retinal astrocytoma with photodynamic therapy.

    PubMed

    Tuncer, Samuray; Cebeci, Zafer

    2014-01-01

    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

  15. Dramatic Regression of Presumed Acquired Retinal Astrocytoma with Photodynamic Therapy

    PubMed Central

    Tuncer, Samuray; Cebeci, Zafer

    2014-01-01

    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

  16. On molecular mechanism of the photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

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

    1995-01-01

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

  17. Three-dimensional illumination procedure for photodynamic therapy of dermatology

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  18. Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy

    PubMed Central

    Denis, Tyler GSt; Hamblin, Michael R

    2013-01-01

    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

  19. Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin

    Microsoft Academic Search

    Rufino M. Silva; João Figueira; M. Luz Cachulo; Liliane Duarte; José R. Faria de Abreu; J. G. Cunha-Vaz

    2005-01-01

    Background  We evaluated, in a nonrandomised, institutional, prospective study, the efficacy of photodynamic therapy (PDT) with verteporfin\\u000a in age-related macular degeneration (AMD) eyes with polypoidal choroidal vasculopathy (PCV) and subfoveal exudation.\\u000a \\u000a \\u000a \\u000a Methods  A prospective clinical and angiographic study was done in 40 consecutive eyes with PCV treated with PDT using masked best-corrected\\u000a visual acuity (VA) and fluorescein and indocyanine green angiographic features

  20. Characterizing low fluence thresholds for in vitro photodynamic therapy

    PubMed Central

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

    2015-01-01

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

  1. Optical Imaging, Photodynamic Therapy and Optically Triggered Combination Treatments.

    PubMed

    Mallidi, Srivalleesha; Spring, Bryan Q; Chang, Sung; Vakoc, Benjamin; Hasan, Tayyaba

    2015-01-01

    Optical imaging is becoming increasingly promising for real-time image-guided resections, and combined with photodynamic therapy (PDT), a photochemistry-based treatment modality, optical approaches can be intrinsically "theranostic." Challenges in PDT include precise light delivery, dosimetry, and photosensitizer tumor localization to establish tumor selectivity, and like all other modalities, incomplete treatment and subsequent activation of molecular escape pathways are often attributable to tumor heterogeneity. Key advances in molecular imaging, target-activatable photosensitizers, and optically active nanoparticles that provide both cytotoxicity and a drug release mechanism have opened exciting avenues to meet these challenges. The focus of the review is optical imaging in the context of PDT, but the general principles presented are applicable to many of the conventional approaches to cancer management. We highlight the role of optical imaging in providing structural, functional, and molecular information regarding photodynamic mechanisms of action, thereby advancing PDT and PDT-based combination therapies of cancer. These advances represent a PDT renaissance with increasing applications of clinical PDT as a frontline cancer therapy working in concert with fluorescence-guided surgery, chemotherapy, and radiation. PMID:26049699

  2. Photodynamic therapy of arteries: preservation of mechanical integrity

    NASA Astrophysics Data System (ADS)

    Grant, William E.; Hopper, Colin; Buonaccorsi, Giovanni A.; Speight, Paul M.; MacRobert, Alexander J.; Fan, Kathleen F.; Bown, Stephen G.

    1995-03-01

    Photodynamic therapy (PDT) of tumors, as a primary treatment or as an adjunctive intra- operative therapy, may expose major vascular structures to injury. PDT has also been proposed to prevent neointimal hyperplasia following angioplasty of stenotic arteries. This study aimed to determine the effect of PDT on the normal rabbit carotid artery, and to determine whether this injury resulted in weakening of the vessel wall. PDT of the carotid arteries of NZW rabbits, using either disulphonated aluminum phthalocyanine or 5- aminolaevulinic acid induced protoporphyrin IX as photosensitizers, was performed using a light dose of 100 J/cm2. Histological examination of the carotids treated with both drugs demonstrated full thickness loss of cellularity 3 days following photodynamic therapy. Treated vessels all remained patent and no inflammatory infiltrate was observed. Elastin van Gieson staining showed preservation of inner and medial elastic laminae and medial and adventitial collagen. Further rabbits were similarly treated with PDT to 1 cm segments of both common carotids and sacrificed at 3, 7, and 21 days. The carotids were exposed and control and treated segments subjected to intraluminal hydrostatic distension until the vessels ruptured. No reduction in the pressure required to rupture the vessels was evident in treated vessels compared with controls. It is concluded that in spite of full thickness cell death, PDT treated arteries are not at risk of thrombotic occlusion or hemorrhage.

  3. Fast elimination of onychomycosis by hematoporphyrin derivative-photodynamic therapy.

    PubMed

    Silva, Ana Paula da; Kurachi, Cristina; Bagnato, Vanderlei Salvador; Inada, Natalia Mayumi

    2013-09-01

    Onychomycosis is a fungal nail disease and is one of the major onychopathy worldwide. Topical or oral antifungal therapies are used to treat this disease, but often they are inefficient and oral medications can even cause several side effects. Photodynamic therapy (PDT) is a well established technique and hence, may represent an alternative non invasive technique for the treatment of onychomycosis. In this work, we present a case of onychomycosis that was completely cured by using the porphyrin-photodynamic therapy. A 59-year-old patient, who had two nails with onychomycosis (the right and the left hallux, with more than thirty and ten years, respectively) caused by fungi was treated once a week for a period of six weeks. The nails were first treated and prepared by a specialist. An hour after the photosensitization, the nail was illuminated using a light source based on light emitting diodes (LEDs) in the red wavelength (630 nm, at a total dose of 54 J/cm(2)). PMID:23993860

  4. Rose bengal acetate photodynamic therapy-induced autophagy.

    PubMed

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

    2010-11-15

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

  5. Bioluminescence-activated deep-tissue photodynamic therapy of cancer.

    PubMed

    Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

    2015-01-01

    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

  6. Continuous low-irradiance photodynamic therapy: a new therapeutic paradigm.

    PubMed

    Rogers, Gary S

    2012-10-01

    A principal factor in determining the biologic consequences of photodynamic therapy (PDT) is the light fluence rate. Preclinical and, more recently, clinical studies have focused on low-irradiance schemes, suggesting that prolonged light exposure, better known as CLIPT (continuous low-irradiance PDT), may improve tumor control while reducing morbidity. After a brief look at the origin of light therapy and photosensitizers, this article turns to the promising animal research supporting the use of low- and ultra-low fluence rate PDT, which serves as the basis of the ongoing CLIPT dosimetry trials for patients with chest wall progression of breast cancer. The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system. PMID:23055207

  7. Photodynamic therapy in combating the causative microorganisms from endodontic infections

    PubMed Central

    de Oliveira, Bruna Paloma; Aguiar, Carlos Menezes; Câmara, Andréa Cruz

    2014-01-01

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

  8. Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

    PubMed Central

    Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

    2015-01-01

    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

  9. Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

    PubMed Central

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

    2014-01-01

    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

  10. Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  11. Measurement of intracellular oxygen concentration during photodynamic therapy in vitro.

    PubMed

    Weston, Mark A; Patterson, Michael S

    2014-01-01

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

  12. Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma

    SciTech Connect

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

    1988-05-01

    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.

  13. Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics

    PubMed Central

    Wang, Chao; Cheng, Liang; Liu, Zhuang

    2013-01-01

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

  14. Illumination devices for photodynamic therapy of the oral cavity

    PubMed Central

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

    2010-01-01

    Three compact and efficient designs are proposed to deliver an average irradiance of 50 mW/cm2 with spatial uniformity well above 90% over a 25 mm2 target area for photodynamic therapy of the oral cavity. The main goal is to produce uniform illumination on the target while limiting irradiation of healthy tissue, thus overcoming the need of shielding the whole oral cavity and greatly simplifying the treatment protocol. The first design proposed consists of a cylindrical diffusing fiber placed in a tailored reflector derived from the edge-ray theorem with dimensions 5.5 × 7.2 × 10 mm3; the second device combines a fiber illuminator and a lightpipe with dimensions 6.8 × 6.8 × 50 mm3; the third design, inspired by the tailored reflector, is based on a cylindrical diffusing fiber and a cylinder reflector with dimensions 5 × 10 × 11 mm3. A prototype for the cylinder reflector was built that provided the required illumination for photodynamic therapy of the oral cavity, producing a spatial uniformity on the target above 94% and an average irradiance of 51 mW/cm2 for an input power of 70 mW. PMID:21157577

  15. Phthalocyanines And Their Sulfonated Derivatives As Photosensitizers In Photodynamic Therapy.

    NASA Astrophysics Data System (ADS)

    Riesz, Peter; Krishna, C. Murali

    1988-02-01

    Photodynamic therapy (PDT) of human tumors with hematoporphyrin derivative (HpD) has achieved encouraging results. However, HpD is a complex mixture whose composition varies in different preparations and with time of storage. The future promise of PDT for cancer treatment depends on the development of new chemically defined sensitizers which absorb more strongly than HpD in the 600-800 nm region. A shift to higher wavelengths is desirable since it allows increased light penetration in human tissues. In vivo, these sensitizers should be non-toxic, localize selectively in tumors and generate cytotoxic species upon illumination with a high quantum yield. These damaging species may be singlet oxygen (1O2) produced by the transfer of energy from the triplet state of the sensitizer to oxygen (Type II) or superoxide anion radicals formed by electron transfer to oxygen or substrate radicals generated by electron or hydrogen transfer directly from the sensitizer (Type I). The recent work of several groups indicating that phthalocyanines and their water soluble derivatives are promising candidates for PDT is reviewed. The photophysics, photochemistry, photosensitized killing of cultured mammalian cells and the use for in vivo photodynamic therapy of phthalocyanines is outlined. Our studies of the post-illumination photohemolysis of human red blood cells as a model system for membrane photomodification sensitized by phthalocyanine sulfonates are consistent with the predominant role of 1O2 as the damaging species.

  16. Adjuvant therapy of colon cancer in idiopathic leukopenia

    Microsoft Academic Search

    Hassan Pervez; Anil Potti; Syed A. Mehdi

    2003-01-01

    Colorectal cancer is a common malignancy. Surgical resection is the primary treatment modality and the outcome is closely\\u000a related to the extent of the disease at presentation. Adjuvant chemotherapy with 5-fluorouracil and leucovorin is the standard\\u000a therapy for resected node-positive disease. This therapy can cause myelosuppression. We present a case of colon cancer with\\u000a idiopathic leukopenia who tolerated chemotherapy without

  17. Physical and mathematical modeling of antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  18. Adjuvant systemic therapy in breast cancer: quo vadis?

    PubMed

    Sonnenblick, A; Piccart, M

    2015-08-01

    The premise that breast cancer (BC) has a tendency toward early systemic dissemination, together with empirical findings showing that drugs given after breast tumor surgery improve outcome, led to the development of systemic adjuvant therapy. This strategy, which started more than 50 years ago, revolutionized BC treatment and improved patient outcome in a substantial way. However, in recent years, several large trials that incorporated new systemic treatments in the adjuvant setting of BC failed to demonstrate a benefit. In the present review, we discuss the progress made in the adjuvant treatment of BC in the past decade, the possible reasons for the recent failures, and practical strategies that may be incorporated in the design of future trials. PMID:25712461

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

    PubMed Central

    Pal, Sumanta K.

    2014-01-01

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

  20. ALA-Butyrate prodrugs for Photo-Dynamic Therapy

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

    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.

  1. Photosensitizer nanocarriers modeling for photodynamic therapy applied to dermatological diseases

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

    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.

  2. Evaluation of photodynamic therapy in adhesion protein expression

    PubMed Central

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

    2014-01-01

    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

  3. In vitro photodynamic therapy on melanoma cell lines with phthalocyanine.

    PubMed

    Kolarova, H; Nevrelova, P; Bajgar, R; Jirova, D; Kejlova, K; Strnad, M

    2007-03-01

    Photodynamic therapy (PDT) is a new treatment modality of tumours. The photochemical interactions of sensitizer, light, and molecular oxygen produce singlet oxygen and other forms of active oxygen, such as peroxide, hydroxyl radical and superoxid anion. Phthalocyanine ClAlPcS(2), belonging among the promising second generation of sensitizers, was tested as an inducer of photodamage. We report the production of reactive oxygen species (ROS) and the phototoxicity of ClAlPcS(2) assessed using G361 melanoma cells. A semiconductor laser (lambda=675nm, output power 21mW) was used as a source for evocation of the photodynamic effect. ROS generation and H(2)O(2) release after PDT on G361 cells were detected using probe CM-H(2)DCFDA and recorded by luminescence spectrometer. Viability studies show, that the optimum phototoxic effect tested on G361 melanoma cells was determined in the combination of laser dose of 25Jcm(-2) and phthalocyanine ClAlPcS(2) concentration of 5microg/ml. This combination of phthalocyanine concentration and corresponding radiation dose was lethal for melanoma cells. PMID:17092686

  4. Role of inflammatory cytokines in the response of solid cancers to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai; Cecic, Ivana; Dougherty, Graeme J.

    2001-04-01

    Photodynamic therapy (PDT) elicits a strong acute inflammatory response that has both local and systemic (acute phase response) attributes. The insult mediated by PDT-induced oxidative stress at the targeted site triggers a complex multifactorial response engaging host defence mechanisms associated with the inflammatory process to participate in the eradication of the treated tumor. Inflammatory cytokines are important mediators of critical events in this process as they regulate the activity of inflammatory, endothelial and other cells. The initial stimulus for enhanced production and release of cytokines likely originates from several types of events, such as activated transcription factors and complement deposition. The PDT-induced complement activation appears to be directly linked to the enhanced expression of various cytokines, including chemokines such as KC (in mouse models), and classic inflammatory cytokines such as IL-1?, TNF-? , IL-6 and IL-10. A variety of interventions that modulate the activity of particular cytokines performed in conjunction with PDT were shown to influence the therapy outcome. The treatments such as using blocking antibodies and local or systemic cytokine delivery may either reduce or dramatically improve the curative effect of PDT. The inflammatory and related cytokines that at present appear particularly interesting and merit further investigation for use as adjuvants to PDT are IL-3, IL-8, IL-15, TNF-?, IFN-?, G-CSF and GM-CSF.

  5. Cyclometalated Ir(III) complexes as targeted theranostic anticancer therapeutics: combining HDAC inhibition with photodynamic therapy.

    PubMed

    Ye, Rui-Rong; Tan, Cai-Ping; He, Liang; Chen, Mu-He; Ji, Liang-Nian; Mao, Zong-Wan

    2014-09-28

    The successful design and anticancer mechanistic studies of a series of cyclometalated Ir(III) complexes with histone deacetylase inhibitory and photodynamic therapy (PDT) activities are reported. PMID:25096019

  6. Antimicrobial Effects of Photodynamic Therapy on Patients with Necrotic Pulps and Periapical Lesion

    Microsoft Academic Search

    Aguinaldo Silva Garcez; Silvia Cristina Nuñez; Michael R. Hamblin; Martha Simões Ribeiro

    2008-01-01

    This study analyzed the antimicrobial effect of photodynamic therapy (PDT) in association with endodontic treatment. Twenty patients were selected. Microbiological samples were taken after accessing the canal, endodontic therapy, and PDT. At the end of the first session, the root canal was filled with Ca(OH)2, and after 1 week, a second session of the therapies was performed. Endodontic therapy gave

  7. [Modern approaches to antimicrobial and anti-inflammatory photodynamic therapy in otorhinolaryngology].

    PubMed

    Lapchenko, A S; Gurov, A V; Kucherov, A G; Order, R Ia; Ioannides, G F

    2014-01-01

    The objective of the present study was to analyse the currently available methods and possibilities for antimicrobial photodynamic therapy (PDT) in medicine with special reference to otorhinolaryngology. The results of the treatment of 300 patients with various suppurative ENT pathologies using antimicrobial PDT were subjected to the analysis. It made it possible to elucidate the mechanisms and parameters of photodynamic treatment and to reveal disadvantages of the modern methods of antimicrobial photodynamic therapy. Special attention is given to the management of acute inflammation in the laryngopharynx and to the topical problems of up-to-date antimicrobial PDT. PMID:24724200

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

    Microsoft Academic Search

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

    2003-01-01

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

  9. Synergistic Anti-Tumor Effects of Combination of Photodynamic Therapy and Arsenic Compound in Cervical Cancer Cells: In Vivo and In Vitro Studies

    PubMed Central

    Kim, Yong-Wan; Bae, Su Mi; Battogtokh, Gantumur; Bang, Hyo Joo; Ahn, Woong Shick

    2012-01-01

    The effects of As4O6 as adjuvant on photodynamic therapy (PDT) were studied. As4O6 is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As4O6 alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% (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. In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As4O6 for inhibition of cervical cancer cell growth. PMID:22715393

  10. Systemic estimation of the effect of photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

    1997-12-01

    The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

  11. Current evidence and applications of photodynamic therapy in dermatology

    PubMed Central

    Wan, Marilyn T; Lin, Jennifer Y

    2014-01-01

    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

  12. [History of photodynamic therapy--past, present and future].

    PubMed

    Kato, H

    1996-01-01

    Photodynamic therapy is achieved by a photodynamic reaction which is induced by excitation of photosensitizer exposed to light. This phenomenon was first reported by Raab et al in 1990. In 1960 Lipson et al reported hematoporphyrin derivative (HpD) by treating hematoporphyrin chloride with hydrochloric acid and sulfuric acid. The development of HpD established the basis of today's photodynamic therapy (PDT). Dougherty reported the treatment of skin tumors by PDT first with an argon dye laser in 1978. The author and his colleagues began basic studies of this treatment using HpD supplied by Dougherty and argon dye laser in canine lung cancer in 1978. These studies confirmed the effectiveness and safety of the method. Bronchofiberscopic PDT for early stage central type squamous cell carcinoma was performed by the authors in 1980 for the first time in the world and complete cure was obtained. Since then PDT has been attracted much attention. The photosensitizer and the laser with a specific wavelength are the key point of PDT. Photofrin, a porfimer sodium (Japan Lederle Co. Ltd., Tokyo, Japan) and excimer dye laser (Hamamatsu Photonics Co. Ltd., Hamamatsu, Japan) obtained governmental approval for clinical use in Japan in 1994, which is equivalent to FDA approval in the US. This method is now used clinically in Canada for certain indications and the Netherlands. In the US it is only approved for compassionate use in cancer of the esophagus. A total of more than 3,000 tumors in the various organs have been treated by PDT so far in 32 countries. The most frequently treated organ is the lung, with 808 cases. A phase II clinical study of PDT for early stage cancer cases of the lung, esophagus, stomach, cervix and urinary bladder was performed in 15 institutions from 1989 to early 1992. The results showed that PDT can successfully treat more than at least 50% of patients with early stage cancer cancer that would otherwise have to be treated by surgery and this means that PDT can contribute to their QOL. The cost effectiveness of PDT versus operation was estimated by the calculation based on QALY's (Quality Adjusted Life Year's saved) by Fujino of the Economics Department of Chuo University. According to this calculation PDT was estimated to be at least 30 percent less than the cost of operation. PDT is indicated in cases with superficial localized early stage lung cancer as a curative treatment and as a palliative treatment for opening stenotic or obstructed bronchi due to tumor prior to the combination therapy with surgery. Recent studies on photodynamic therapy (PDT) began just two decades ago, therefore there are still a large number of unsolved problems. However PDT will have many applications in a wide range of fields from preclinical to clinical medical science. In lung cancer, the indications will be extended for early stage lung cancer and improvement of therapeutic results will be achieved by the development of new photosensitizers such as chlorin, pheophorbide, phthalocyanin, ALA, benzoporphyrin, etc which can be excited by longer wavelength and new lasers such as pulsed excimer dye, YAG-OPO and diode lasers. Through these new developments the indications of this treatment for malignant will continue to expand. PMID:8546474

  13. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

    NASA Astrophysics Data System (ADS)

    Kishen, Anil; George, Saji

    2013-02-01

    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.

  14. 5-ALA-assisted photodynamic therapy in canine prostates

    NASA Astrophysics Data System (ADS)

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

    1996-05-01

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

  15. Photodynamic therapy in dermatology: past, present, and future

    NASA Astrophysics Data System (ADS)

    Darlenski, Razvigor; Fluhr, Joachim W.

    2013-06-01

    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.

  16. Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    PubMed

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

    2014-09-01

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

  18. Calcium phosphosilicate nanoparticles for imaging and photodynamic therapy of cancer.

    PubMed

    Tacelosky, Diana M; Creecy, Amy E; Shanmugavelandy, Sriram S; Smith, Jill P; Claxton, David F; Adair, James H; Kester, Mark; Barth, Brian M

    2012-04-01

    Photodynamic therapy (PDT) has emerged as an alternative modality for cancer treatment. PDT works by initiating damaging oxidation or redox-sensitive pathways to trigger cell death. PDT can also regulate tumor angiogenesis and modulate systemic antitumor immunity. The drawbacks to PDT--photosensitizer toxicity, a lack of selectivity and efficacy of photosensitizers, and a limited penetrance of light through deep tissues--are the same pitfalls associated with diagnostic imaging. Developments in the field of nanotechnology have generated novel platforms for optimizing the advantages while minimizing the disadvantages of PDT. Calcium phosphosilicate nanoparticles (CPSNPs) represent an optimal nano-system for both diagnostic imaging and PDT. In this review, we will discuss how CPSNPs can enhance optical agents and serve as selective, non-toxic, and functionally stable photosensitizers for PDT. We will also examine novel applications of CPSNPs and PDT for the treatment of leukemia to illustrate their potential utility in cancer therapeutics. PMID:22541615

  19. Photodynamic therapy induces an immune response against a bacterial pathogen.

    PubMed

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

    2012-07-01

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

  20. Photodynamic therapy for head and neck lesions in the subtropics.

    PubMed

    Civantos, Francisco

    2012-10-01

    Surgery, radiotherapy, and chemotherapy remain standard treatment options for patients with head and neck carcinomas, but because they are often associated with complications, there is room for improvement. Although not widely practiced and still off-label, photodynamic therapy (PDT) is a promising alternative for superficial malignant or premalignant lesions of the upper aerodigestive tract. It also may be useful for those with recurrent surface disease after surgery or radiotherapy. After an historic look at the data on PDT for head and neck tumors, this article offers a current perspective from a fairly selective PDT program that has achieved dramatic lasting responses. Where PDT may fit in the treatment spectrum for head and neck cancers is one of the unanswered questions requiring further study. PMID:23055220

  1. Photodynamic therapy with Photofrin II by bronchial artery infusion

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

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

  2. Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue.

    PubMed

    Kariminezhad, H; Habibi, M; Mirzababayi, N

    2015-07-01

    Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV-Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mgg(-1)). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency. PMID:25900556

  3. Laser Doppler flowmetry in photodynamic therapy on xenotransplanted tumors

    NASA Astrophysics Data System (ADS)

    Vervoorts, Anja; Rood, H. A.; Moser, Joerg G.; Klotz, Marcus

    1996-05-01

    Perfusion of tumor tissue is a necessary prerequisite for radiotherapy and Photodynamic Tumor Therapy (PDT). For PDT perfusion means oxygen supply to a light activated photosensitizing drug inside tumor cells to destroy these cells specifically by light activated singlet oxygen. These experiments are normally done in rodents, but can be much more easily performed on tumors transplanted to the extraembryonal painfree vessels developed during chick embryogenesis. We chose the yolk sac membrane and the chorioallantoic membrane for quantitative blood flow measurements. Near infrared light (830 nm) was used for measurements in vascularized xenotransplanted tumors on the extraembryonal membranes because at this wavelength blood flow can be detected also in vessels covered by tumor cells. We measured the influences on blood flow of different photosensitizers with and without therapeutic irradiation and single components of a polyphasic PDT System.

  4. Photodynamic therapy of head and neck cancer with different sensitizers

    NASA Astrophysics Data System (ADS)

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

    1997-12-01

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

  5. Photodynamic therapy induces an immune response against a bacterial pathogen

    PubMed Central

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

    2012-01-01

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

  6. Effects of photodynamic therapy on human glioma spheroids

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Sun, Chung-Ho; Chu, Eugene A.; Hirschberg, Henry; Tromberg, Bruce J.

    1999-07-01

    The poor prognosis for patients with malignant brain neoplasm has led to a search for better treatment modalities. Although gliomas are considered to be disseminated tumors in the brain, most recur at the site of the previous tumor resection. Improved local control would thus be of clear benefit. The utility of photodynamic therapy (PDT) in the treatment of brain neoplasms is investigated using a human glioma spheroid model. Specifically, the effects of PDT on human glioma spheroids are investigated using PhotofrinTM and 56-aminolevulinic acid (ALA). The effects of various irradiation schemes were monitored using a simple growth assay. A growth delay was observed at an optical fluence of approximately 35 J cm-2 for spheroids incubated in Photofrin. Spheroids incubated in ALA were unaffected by the PDT treatment regimens examined in this study. This was most likely a result of inadequate photosensitizer concentration.

  7. TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wilson, Brian C.; Patterson, Michael S.

    2008-05-01

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components—light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

  8. Photodynamic therapy in Barrett's esophagus: review of current results

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Overholt, Bergein F.

    1996-04-01

    Photodynamic therapy has been established as an alternative treatment for patients with Barrett's esophagus with dysplasia or early superficial cancer. Twenty-three patients have been treated and followed for 6 - 54 months. Twenty-one patients had high grade dysplasia and 2 had low grade dysplasia. Ten patients had early cancer (Tis-T1) and 1 had T2 cancer. All patients were maintained on omeprazole after treatment. Three separate PDT treatments were required in 2 patients, 2 in 5 patients and 1 in 16. Dysplasia and carcinoma were eliminated in all. Seventy-five to eighty percent of Barrette's mucosa was replaced by squamous epithelium. One patient developed a new carcinoma in an area of dysplasia treated 3 months earlier and was retreated successfully. Two patients developed new areas of dysplasia in untreated segments of the Barrett's esophagus, requiring a separate treatment. Twelve patients developed strictures, all responding well to dilatation.

  9. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

    PubMed Central

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

    2013-01-01

    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

  10. The Disinfecting Efficacy of Root Canals with Laser Photodynamic Therapy

    PubMed Central

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

    2014-01-01

    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

  11. Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy.

    PubMed

    Yuan, Ahu; Yang, Bing; Wu, Jinhui; Hu, Yiqiao; Ming, Xin

    2015-07-15

    Application of photodynamic therapy for treating cancers has been restrained by suboptimal delivery of photosensitizers to cancer cells. Nanoparticle (NP)-based delivery has become an important strategy to improve tumor delivery of photosensitizers; however, the success is still limited. One problem for many NPs is poor penetration into tumors, and thus the photokilling is not complete. We aimed to use chemical conjugation method to engineer small NPs for superior cancer cell uptake and tumor penetration. Thus, Chlorin e6 (Ce6) was covalently conjugated to PAMAM dendrimer (generation 7.0) that was also modified by tumor-targeting RGD peptide. With multiple Ce6 molecules in a single nanoconjugate molecule, the resultant targeted nanoconjugates showed uniform and monodispersed size distribution with a diameter of 28nm. The singlet oxygen generation efficiency and fluorescence intensity of the nanoconjugates in aqueous media were significantly higher than free Ce6. Targeted nanoconjugates demonstrated approximately 16-fold enhancement in receptor-specific cellular delivery of Ce6 into integrin-expressing A375 cells compared to free Ce6 and thus were able to cause massive cell killing at low nanomolar concentrations under photo-irradiation. In contrast, they did not cause significant toxicity up to 2?M in dark. Due to their small size, the targeted nanoconjugates could penetrate deeply into tumor spheroids and produced strong photo-toxicity in this 3-D tumor model. As a result of their great cellular delivery, small size, and lack of dark cytotoxicity, the nanoconjugates may provide an effective tool for targeted photodynamic therapy of solid tumors. PMID:25900441

  12. System for integrated interstitial photodynamic therapy and dosimetric monitoring

    NASA Astrophysics Data System (ADS)

    Johansson, Ann; Soto Thompson, Marcelo; Johansson, Thomas; Bendsoe, Niels; Svanberg, Katarina; Svanberg, Sune; Andersson-Engels, Stefan

    2005-04-01

    Photodynamic therapy for the treatment of cancer relies on the presence of light, sensitizer and oxygen. By monitoring these three parameters during the treatment a better understanding and treatment control could possibly be achieved. Here we present data from in vivo treatments of solid skin tumors using an instrument for interstitial photodynamic therapy with integrated dosimetric monitoring. By using intra-tumoral ALA-administration and interstitial light delivery solid tumors are targeted. The same fibers are used for measuring the fluence rate at the treatment wavelength, the sensitizer fluorescence and the local blood oxygen saturation during the treatment. The data presented is based on 10 treatments in 8 patients with thick basal cell carcinomas. The fluence rate measurements at 635 nm indicate a major treatment induced absorption increase, leading to a limited light penetration at the treatment wavelength. This leads to a far from optimal treatment since the absorption increase prevents peripheral tumor regions from being fully treated. An interactive treatment has been implemented assisting the physician in delivering the correct light dose. The absorption increase can be compensated for by either prolonging the treatment time or increasing the output power of each individual treatment fiber. The other parameters of importance, i.e. the sensitizer fluorescence at 705 nm and the local blood oxygen saturation, are monitored in order to get an estimate of the amount of photobleaching and oxygen consumption. Based on the oxygen saturation signal, a fractionized irradiation can be introduced in order to allow for a re-oxygenation of the tissue.

  13. [Research progress of the anti-tumor effect of sonodynamic and photodynamic therapy].

    PubMed

    Su, Xiaomin; Li, Long; Wang, Pan

    2012-06-01

    Cancer, as a serious threat to human health, is one of the major killers. The treatment of cancer has attracted more and more attention. Currently, the means of treating cancer is also increasing, but there is no emergence of a fully satisfactory treatment. A combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT), named sono-photodynamic therapy (S-PDT), is a new composite cancer therapy. Because the therapy can significantly improve the tumor curing effect, it has good application prospects in cancer prevention and treatment. The present article reviewed the progress of the anti-tumor mechanisms and influencing factors of S-PDT. PMID:22826963

  14. Photodynamic methods for fluorescence diagnosis and therapy of photosensitized tumors

    NASA Astrophysics Data System (ADS)

    Unsoeld, Eberhard

    1992-03-01

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

  15. Advance in photosensitizers and light delivery for photodynamic therapy.

    PubMed

    Yoon, Il; Li, Jia Zhu; Shim, Young Key

    2013-01-01

    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

  16. Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

    PubMed Central

    Yoon, Il; Li, Jia Zhu

    2013-01-01

    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

  17. Optimization of light sources for prostate photodynamic therapy

    PubMed Central

    Altschuler, Martin D.; Zhu, Timothy C; Li, Jun; Hahn, Stephen M

    2015-01-01

    To deliver uniform photodynamic dose to the prostate gland, it is necessary to develop algorithms that optimize the location and strength (emitted power × illumination time) of each light source. Since tissue optical properties may change with time, rapid (almost real-time) optimization is desirable. We use the Cimmino algorithm because it is fast, linear, and always converges reliably. A phase I motexafin lutetium (MLu)-mediated photodynamic therapy (PDT) protocol is on-going at the University of Pennsylvania. The standard plan for the protocol uses equal source strength and equal spaced loading (1-cm). PDT for the prostate is performed with cylindrical diffusing fibers (CDF) of various lengths inserted to longitudinal coverage within the matrix of parallel catheters perpendicular to a base plate. We developed several search procedures to aid the user in choosing the positions, lengths, and intensities of the CDFs. The Cimmino algorithm is used in these procedures to optimize the strengths of the light catheters at each step of the iterative selection process. Maximum and minimum bounds on allowed doses to points in four volumes (prostate, urethra, rectum, and background) constrain the solutions for the strengths of the linear light sources. Uniform optical properties are assumed. To study how different opacities of the prostate would affect optimization, optical kernels of different light penetration were used. Another goal is to see whether the urethra and rectum can be spared, with minimal effect on PTV treatment delivery, by manipulating light illumination times of the sources. Importance weights are chosen beforehand for organ volumes, and normalized. Compared with the standard plan, our algorithm is shown to produce a plan that better spares the urethra and rectum and is very fast. Thus the combined selection of positions, lengths, and strengths of interstitial light sources improves outcome.

  18. Optimization of light sources for prostate photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Altschuler, Martin D.; Zhu, Timothy C.; Li, Jun; Hahn, Stephen M.

    2005-04-01

    To deliver uniform photodynamic dose to the prostate gland, it is necessary to develop algorithms that optimize the location and strength (emitted power × illumination time) of each light source. Since tissue optical properties may change with time, rapid (almost real-time) optimization is desirable. We use the Cimmino algorithm because it is fast, linear, and always converges reliably. A phase I motexafin lutetium (MLu)-mediated photodynamic therapy (PDT) protocol is on-going at the University of Pennsylvania. The standard plan for the protocol uses equal source strength and equal spaced loading (1-cm). PDT for the prostate is performed with cylindrical diffusing fibers (CDF) of various lengths inserted to longitudinal coverage within the matrix of parallel catheters perpendicular to a base plate. We developed several search procedures to aid the user in choosing the positions, lengths, and intensities of the CDFs. The Cimmino algorithm is used in these procedures to optimize the strengths of the light catheters at each step of the iterative selection process. Maximum and minimum bounds on allowed doses to points in four volumes (prostate, urethra, rectum, and background) constrain the solutions for the strengths of the linear light sources. Uniform optical properties are assumed. To study how different opacities of the prostate would affect optimization, optical kernels of different light penetration were used. Another goal is to see whether the urethra and rectum can be spared, with minimal effect on PTV treatment delivery, by manipulating light illumination times of the sources. Importance weights are chosen beforehand for organ volumes, and normalized. Compared with the standard plan, our algorithm is shown to produce a plan that better spares the urethra and rectum and is very fast. Thus the combined selection of positions, lengths, and strengths of interstitial light sources improves outcome.

  19. Directed molecular assembly into a biocompatible photosensitizing nanocomplex for locoregional photodynamic therapy.

    PubMed

    Lee, Yong-Deok; Cho, Hong-Jun; Choi, Mi-Hwa; Park, Hoyong; Bang, Joona; Lee, Sangyoup; Kwon, Ick Chan; Kim, Sehoon

    2015-07-10

    Methylene blue (MB), a water-soluble cationic dye widely used in the clinic, is known to photosensitize the generation of cytotoxic singlet oxygen efficiently, and thus, has attracted interest as a potential drug for photodynamic therapy (PDT). However, its use for the in vivo PDT of cancer has been limited due to the inherently poor cell/tissue accumulation and low biological stability in the free molecular form. Here, we report a simple and biocompatible nanocomplex formulation of MB (NanoMB) that is useful for in vivo locoregional cancer treatment by PDT. NanoMB particles were constructed through the self-assembly of clinically usable molecules (MB, fatty acid and a clinically approved polymer surfactant) directed by the dual (electrostatic and hydrophobic) interactions between the ternary constituents. The nanocomplexed MB showed greatly enhanced cell internalization while keeping the photosensitization efficiency as high as free MB, leading to distinctive phototoxicity toward cancer cells. When administered to human breast cancer xenograft mice by peritumoral injection, NanoMB was capable of facile penetration into the tumor followed by cancer cell accumulation, as examined in vivo and histologically with the near-infrared fluorescence signal of MB. The quintuple PDT treatment by a combination of peritumorally injected NanoMB and selective laser irradiation suppressed the tumor volume efficaciously, demonstrating potential of NanoMB-based PDT as a biocompatible and safe method for adjuvant locoregional cancer treatment. PMID:25872152

  20. Antimicrobial photodynamic therapy and photodynamic inactivation, or killing bugs with dyes and light--a symposium-in-print.

    PubMed

    Hamblin, Michael R

    2012-01-01

    In antimicrobial photodynamic therapy, the photosensitizer (PS) in its ground singlet state absorbs light to give the excited singlet state that can transition to the long-lived triplet state. This PS triplet may undergo energy transfer (Type 2) or electron transfer (Type 1) to oxygen to form reactive oxygen species (singlet oxygen and/or hydroxyl radicals) that can kill both Gram-positive and Gram-negative bacteria and fungi. Infections in animal models can also be treated. PMID:22497420

  1. Strategies to potentiate immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2015-03-01

    Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical 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 a great potential to become more widely used. Although the stimulation of tumorspecific 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. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. Other promising approaches involve depleting regulatory T-cells and epigenetic reversal agents. 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.

  2. Cell Death Pathways in Photodynamic Therapy of Cancer

    PubMed Central

    Mroz, Pawel; Yaroslavsky, Anastasia; Kharkwal, Gitika B; Hamblin, Michael R.

    2011-01-01

    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 localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT. PMID:23914299

  3. Effects of photodynamic therapy on Enterococcus faecalis biofilms.

    PubMed

    López-Jiménez, L; Fusté, E; Martínez-Garriga, B; Arnabat-Domínguez, J; Vinuesa, T; Viñas, M

    2015-07-01

    Microbial biofilms are involved in almost all infectious pathologies of the oral cavity. This has led to the search for novel therapies specifically aimed at biofilm elimination. In this study, we used atomic force microscopy (AFM) to visualize injuries and to determine surface roughness, as well as confocal laser scanning microscopy (CLSM) to enumerate live and dead bacterial cells, to determine the effects of photodynamic therapy (PDT) on Enterococcus faecalis biofilms. The AFM images showed that PDT consisting of methylene blue and a 670-nm diode laser (output power 280 mW during 30 s) or toluidine blue and a 628-nm LED light (output power 1000 mW during 30 s) induced severe damage, including cell lysis, to E. faecalis biofilms, with the former also causing an important increase in surface roughness. These observations were confirmed by the increase in dead cells determined using CLSM. Our results highlight the potential of PDT as a promising method to achieve successful oral disinfection. PMID:25917515

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

    PubMed

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

    2014-11-17

    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

  5. Photodynamic therapy of non-melanoma skin cancers

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

    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.

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

    PubMed Central

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

    2008-01-01

    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

  7. Core – shell upconversion nanoparticle – semiconductor heterostructures for photodynamic therapy

    PubMed Central

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

    2015-01-01

    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

  8. Monte Carlo modelling of daylight activated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Campbell, C. L.; Wood, K.; Valentine, R. M.; Brown, C. T. A.; Moseley, H.

    2015-05-01

    The treatment of superficial skin lesions via daylight activated photodynamic therapy (PDT) has been explored theoretically with three dimensional (3D) Monte Carlo radiation transfer simulations. For similar parameters and conditions, daylight activated PDT was compared to conventional PDT using a commercially available light source. Under reasonable assumptions for the optical properties of the tissue, protoporphyrin IX (PpIX) concentration and a treatment dose of 75 J cm?2, it was found that during a clear summer day an effective treatment depth of over 2 mm can be achieved after 30 min of daylight illumination at a latitude of 56 degrees North. The same light dose would require 2.5 h of daylight illumination during an overcast summer day where a treatment depth of about 2 mm can be achieved. For conventional PDT the developed model suggests that 15 min of illumination is required to deliver a light dose of 75 J cm?2, which would result in an effective treatment depth of about 3 mm. The model developed here allows for the determination of photo-toxicity in skin tissue as a function of depth for different weather conditions as well as for conventional light sources. Our theoretical investigation supports clinical studies and shows that daylight activated PDT has the potential for treating superficial skin lesions during different weather conditions.

  9. Monte Carlo modelling of daylight activated photodynamic therapy.

    PubMed

    Campbell, C L; Wood, K; Valentine, R M; Brown, C T A; Moseley, H

    2015-05-21

    The treatment of superficial skin lesions via daylight activated photodynamic therapy (PDT) has been explored theoretically with three dimensional (3D) Monte Carlo radiation transfer simulations. For similar parameters and conditions, daylight activated PDT was compared to conventional PDT using a commercially available light source. Under reasonable assumptions for the optical properties of the tissue, protoporphyrin IX (PpIX) concentration and a treatment dose of 75 J cm(-2), it was found that during a clear summer day an effective treatment depth of over 2 mm can be achieved after 30 min of daylight illumination at a latitude of 56 degrees North. The same light dose would require 2.5 h of daylight illumination during an overcast summer day where a treatment depth of about 2 mm can be achieved. For conventional PDT the developed model suggests that 15 min of illumination is required to deliver a light dose of 75 J cm(-2), which would result in an effective treatment depth of about 3 mm. The model developed here allows for the determination of photo-toxicity in skin tissue as a function of depth for different weather conditions as well as for conventional light sources. Our theoretical investigation supports clinical studies and shows that daylight activated PDT has the potential for treating superficial skin lesions during different weather conditions. PMID:25927971

  10. Photodynamic Therapy and the Development of Metal-Based Photosensitisers

    PubMed Central

    Josefsen, Leanne B.; Boyle, Ross W.

    2008-01-01

    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

  11. Differential cell photosensitivity in photodynamic therapy of the rat endometrium

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

    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.

  12. Photodynamic therapy in thoracic oncology: a single institution experience

    NASA Astrophysics Data System (ADS)

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

    2001-04-01

    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.

  13. An update on photodynamic therapies in the treatment of onychomycosis.

    PubMed

    Simmons, B J; Griffith, R D; Falto-Aizpurua, L A; Nouri, K

    2015-07-01

    Onychomycosis is a common fungal infection of the nails that is increasing in prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a therapeutic challenge that can lead to significant reductions in quality of life leading to both physical and psychological consequences. Current treatment modalities are difficult to implement due to the poor penetration of topical treatments to the nail bed, the slow growing nature of nails and the need for prolonged use of topical and/or oral medications. Standard of care medications have cure rates of 63-76% that leads to a high propensity of treatment failures and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and aminolevulinic acid (ALA) have been used as photosensitizers with approximately 630 nm light. These modalities are combined with pre-treatment of urea and/or microabrasion for better penetration. PDT treatments are well tolerated with only mild transient pain, burning and erythema. In addition, significant cure rates for patients who have contraindications to oral medications or failed standard medications can be obtained. With further enhancements in photosensitizer permeability, decreased pre-treatment and photosensitizer incubation times, PDT can be a more efficient and cost-effective in office based treatment for onychomycosis. However, more large-scale randomized control clinical trials are needed to access the efficacy of PDT treatments. PMID:25589056

  14. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

    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.

  15. Lung Cancers Treated With Photodynamic Therapy and Surgery

    PubMed Central

    Hiyoshi, Toshimitsu; Furukawa, Kinya; Yamamoto, Hideki; Tsuchida, Takaaki; Usuda, Jitsuo; Kumasaka, Hideo; Ishida, Junzou; Konaka, Chimori; Kato, Harubumi

    1999-01-01

    Laser endoscopic surgery, especially the effectiveness of photodynamic therapy (PDT) using Photofrin as a photosensitizer, has now achieved a status as effective treatment modality for lung cancer. Twenty-six lung cancer patients received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. Bronchoscopical PDT is performed with topical anesthesia approximately 48 h after the intravenous injection of 2.0 mg/kg body weight of Photofrin. Operation was performed 2–9 weeks after initial PDT. The initial purpose of PDT, i.e. either to reduce the extent of resection or convert inoperable disease to operable status, was achieved in 22 out of 26 patients treated. The survival rate of T3 (main bronchus invasion) cases treated by surgery alone increased significantly from 50.9% to 60.0% with the application of preoperative PDT. This remarkable result may imply that this new option of PDT as preoperative laser irradiation may contribute to the management of advanced lung malignancy. PMID:18493497

  16. Characterizing light propagation in bone for photodynamic therapy of osteosarcoma

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  17. Synthesis of folate receptor-targeted photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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-).

  18. Cationic porphyrin derivatives for application in photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    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

    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.

  19. Photodynamic therapy and fluorescent diagnostics of breast cancer

    NASA Astrophysics Data System (ADS)

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

    2004-06-01

    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.

  20. Model for monitoring the process of photodynamic therapy in patients

    NASA Astrophysics Data System (ADS)

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

    2005-07-01

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

  1. Application of chemiluminescence with FCLA in photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2005-01-01

    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.

  2. Tumor vascular microenvironment determines responsiveness to photodynamic therapy.

    PubMed

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

    2012-04-15

    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 showed 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 show 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

  3. Safety assessment of oral photodynamic therapy in rats.

    PubMed

    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

    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

  4. Mechanisms of tumor destruction caused by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhou, Chuannong

    2005-07-01

    Photodynamic therapy is a relatively new treatment modality and is becoming widely accepted as a standard treatment of a variety of solid tumors. This includes palliative treatments for advanced or obstructive cancers in many organs as well as a curative treatment for some early cancers and pre-cancerous lesions. It has been approved by health authorities in a number of countries in America, Europe and Asia [1]. PDT is a procedure requiring 3 elements: photosensitizer, light and oxygen [2]. The typical technique involves an intravenous administration of a photosensitizing agent, which is preferentially accumulated or retained in tumor tissue, followed by irradiation of the tumor area with light of appropriate wavelength. In the presence of oxygen it generates highly reactive and cytotoxic molecular species, in particular, singlet oxygen (1O2), which may oxidize various bio-molecules and finally leading to cell death and tumor destruction [3]. The most widely used photosensitizer in clinical treatment of cancers is Photofrin (porfimer sodium), and most widely used light sources are lasers of various types, in recent years preferentially, diode laser, which emits a red light of 630 nm wavelength.

  5. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  6. Photodynamic therapy for malignant tumours of the ampulla of Vater.

    PubMed Central

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

    1995-01-01

    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

  7. Five years experience of photodynamic therapy with new chlorin photosensitizer

    NASA Astrophysics Data System (ADS)

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

    2005-08-01

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

  8. Fluorescence guided evaluation of photodynamic therapy as acne treatment

    NASA Astrophysics Data System (ADS)

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

    2005-08-01

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

  9. Solid state lasers for photodynamic therapy of malignant neoplasm

    NASA Astrophysics Data System (ADS)

    Khulugurov, Vitaliy M.; Ivanov, Nikolai; Kim, Byoung-Chul; Mayorov, Alexander; Bordzilovsky, Dnitri; Masycheva, Valentina; Danilenko, Elena; Chung, Moon-Kwan

    2002-05-01

    This work demonstrates the possibility of treating animals with malignant neoplasms using 608 nm of laser radiation by means of photodynamic therapy (PDT). The intracavity transformation of the Nd:YAP main radiation 1079 nm was Raman converted in barium nitrate crystal, and the Stokes frequency (1216 nm) was doubled using KTP or RTA crystals. The LiF or Cr:YAG crystals are used for the Q-switch. The radiation parameters were obtained at 100 Hz pump repetition frequency. The average power at 608-nm radiation with LiF and KTP was 700 mW at multimode generation. The 3-6 single 10-15 ns pulses were generated during one cycle of pumping. The doubling efficiency with RTA was two times more than with KTP. The cells of Ehrlich adenocarcinoma (0.1 ml) were implanted in hind thighs of ICR white non-imbred mice. Photosensitizer HpD was i.v. administered in a dose of 10 mg/kg. Ten animals were treated (2 as a control). There was a 9-30% decrease in the tumor growth depending on the irradiation dose. The better result (30%) was for the 200 J/cm2 dose radiation. These results show the possibility of using all solid state lasers with wavelength of 608 nm for PDT.

  10. Photodynamic therapy-induced apoptosis of HeLa cells.

    PubMed

    Panzarini, Elisa; Tenuzzo, Bernardetta; Dini, Luciana

    2009-08-01

    Photodynamic therapy (PDT), which is a treatment for cancer and certain noncancerous conditions, requires exposure of cells or tissue to a photosensitizing drug followed by irradiation with visible light of the appropriate wavelength. By using Rose Bengal Acetate (RBAc) as the photosensitizer and an innovative green light-emitting diode, we investigated the efficiency with which apoptosis is induced in HeLa cells, focusing our study on mitochondria alteration and cytochrome c release. Indeed, RBAc is a very efficient fluorogenic substrate and easily enters the cells where the original photoactive molecule is restored by specific esterases. HeLa cells after PDT underwent a consistent rate of apoptosis (peaked at 12 h of recovery post-PDT). Necrosis was observed at the longest times of recovery as a result of secondary necrosis. PDT gave rise to a series of shape modifications, mainly referable to apoptotic-related changes (i.e., extensive blebs formation) involving both F-actin and tubulin networks. Soon after PDT, mitochondria lose their potential membranes and release large quantities of cytochrome c. PMID:19723112

  11. Photodynamic therapy of dysplasia in Barrett's esophagus: an update

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Overholt, Bergein F.

    1997-05-01

    Photodynamic therapy using Photofrin has been used as an alternative to esophagectomy for patients with dysplasia or superficial cancer associated with Barrett's esophagus. In this update we present the results in 71 patients treated and followed for 6-72 months. 54 patients had high grade dysplasia/early cancer, and 17 had low grade dysplasia. 22 Patients had early cancer and 1 had T2 cancer. Three separate PDT treatments were required in 3 patients, 2 in 20 patients and 1 in 48. All patients were maintained on omeprazole. Patients received a photofrin dose of 2 mg/kg followed two days later by 630 nm laser light from an either argon/dye laser or KTP/dye laser. The majority of patients received light from a balloon light delivery device. Dysplasia and carcinoma was eliminated or reduced in majority of the cases. 75-80 percent of Barrett's mucosa was replaced by squamous epithelium. 34 patients developed strictures. All responded well to dilation.

  12. Four-year clinical experience in photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1996-12-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of skin, breasts, tongue, oral mucose, lower lip, larynx, stomach, bladder, rectum and other locations has been made. During 1992 - 1996 867 tumoral foci in 222 patients have been treated with PDT. All patients were previously treated with conventional techniques 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. Up to now we have follow-up control data within 2 months and 4 years. Positive effect of PDT was seen in 93.7% of patients including complete regression of tumors in 64.9% and partial in 28.8%. 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.

  13. Treatment of oral lichen planus with photodynamic therapy mediated methylene blue: A case report

    Microsoft Academic Search

    Farzane Aghahosseini; Fateme Arbabi-Kalati; Leila Ataie Fashtami; Mohsen Fateh; Gholamreza Esmaeeli Djavid

    Oral lichen planus (OLP) is a common chronic disease of uncertain origin. Many patients with OLP are refractory to all available therapies. The photodynamic therapy (PDT) was used as a possible alternative method in the treatment of lichen planus. Two patients with five oral lichen planus lesions were treated using topical PDT mediated by methylene blue (MB-PDT). The patients were

  14. Methylaminolaevulinic Acid Photodynamic Therapy in the Treatment of Erythroplasia of Queyrat

    Microsoft Academic Search

    Laurence Feldmeyer; Valérie Krausz-Enderlin; Bettina Töndury; Jürg Hafner; Lars E. French; Günther F. L. Hofbauer

    2011-01-01

    Background: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the penis. Progression to invasive carcinoma may occur. Its cause is unknown but some evidence suggests infection with human papillomavirus in the pathogenesis of EQ; however, recent data do not confirm this. Therapy is difficult and associated with important recurrence rates. Photodynamic therapy (PDT) employs a photosensitizer excited by visible

  15. Induction of Immune Mediators in Glioma and Prostate Cancer Cells by Non-Lethal Photodynamic Therapy

    Microsoft Academic Search

    Robert Kammerer; Alexander Buchner; Patrick Palluch; Thomas Pongratz; Konstantin Oboukhovskij; Wolfgang Beyer; Ann Johansson; Herbert Stepp; Reinhold Baumgartner; Wolfgang Zimmermann; Joseph Najbauer

    2011-01-01

    BackgroundPhotodynamic therapy (PDT) uses the combination of photosensitizing drugs and harmless light to cause selective damage to tumor cells. PDT is therefore an option for focal therapy of localized disease or for otherwise unresectable tumors. In addition, there is increasing evidence that PDT can induce systemic anti-tumor immunity, supporting control of tumor cells, which were not eliminated by the primary

  16. Photodynamic therapy of virus-associated epithelial tumours of the face in organ transplant recipients

    Microsoft Academic Search

    Peter Schleier; Peter Hyckel; Alexander Berndt; Hans-Peter Bode; Volker Albrecht; Winfried Hindermann; Hartwig Kosmehl; Witold Zenk; Dieter Schumann

    2004-01-01

    Purpose The benefit for organ recipients is still counteracted by the side effects of immunosuppression. Among other effects, there is a 50–250 times increased risk of developing malignant skin tumours. Because these malignomas are known to develop particularly aggressivly, there is a special need for an efficient therapy. Here we demonstrate the treatment response to aminolaevulinic acid (ALA)-based photodynamic therapy

  17. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

    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.

  18. Photodynamic therapy of cancer: five-year clinical experience

    NASA Astrophysics Data System (ADS)

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

    1997-12-01

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

  19. Common adjuvant breast cancer therapies do not inhibit cancer vaccine induced T cell immunity

    Microsoft Academic Search

    Andrew L. Coveler; Vivian Goodell; Devon J. Webster; Lupe G. Salazar; Patricia A. Fintak; Jennifer S. Childs; Doreen M. Higgins; Mary L. Disis

    2009-01-01

    s  Cancer vaccines may have the most potential for clinical impact when used in the adjuvant setting when tumor burden is at\\u000a its lowest. Application of cancer vaccines in the adjuvant setting, however, requires integration of immunization with more\\u000a standard cytotoxic or cytostatic therapies. Common adjuvant therapies for breast cancer patients, i.e. trastuzumab, bisphosphonates\\u000a and hormonal agents are often administered over

  20. A new method for photodynamic therapy of melanotic melanoma -- effects of depigmentation with violet light photodynamic therapy.

    PubMed

    Ma, Li-Wei; Nielsen, Kristian Pagh; Iani, Vladimir; Moan, Johan

    2007-01-01

    Melanotic melanomas have a poor response to photodynamic therapy (PDT). The reason for this is that melanin absorbs light over the entire wavelength region used for PDT (400-750 nm). Photobleaching of melanin is an approach to overcome this obstacle. In the present work, reflectance spectroscopy was applied to study depigmentation of human and murine skin with different melanin contents, and effects induced by PDT with topical application of methyl 5-aminolevulinate (MAL) on B16F10 melanotic melanomas transplanted to nude mice. Depigmentation and inhibition of tumor growth after violet light (420 nm) exposure, red light (634 nm) exposure, and combinations of both were studied. Reflectance spectroscopy was suitable for evaluation of the pigmentation of both human and murine skin. Skin depigmentation leads to increase in reflectance. PDT with violet light bleached some of the melanin in the skin above the B16F10 melanomas, and possibly also in the upper part of the melanomas. This resulted in a larger growth inhibition of tumors first given PDT with violet light and then with red light compared to treatments using the reverse order of illumination, namely, red light before violet light. It is concluded that violet light PDT can bleach melanin in melanotic tumors and therefore increase their sensitivity to red light PDT. This finding indicates a new PDT modality that can be further developed for treatment of superficial melanotic melanomas and possibly other diseases where pigmentation is a problem. PMID:18197832

  1. Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment.

    PubMed

    Chen, Hongmin; Wang, Geoffrey D; Chuang, Yen-Jun; Zhen, Zipeng; Chen, Xiaoyuan; Biddinger, Paul; Hao, Zhonglin; Liu, Feng; Shen, Baozhong; Pan, Zhengwei; Xie, Jin

    2015-04-01

    Photodynamic therapy is a promising treatment method, but its applications are limited by the shallow penetration of visible light. Here, we report a novel X-ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised of a core of a nanoscintillator and a mesoporous silica coating loaded with photosensitizers, converts X-ray photons to visible photons to activate the photosensitizers and cause efficient tumor shrinkage. PMID:25756781

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

    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.

  3. The impact of laser irradiation during antimicrobial photodynamic therapy in an artificial biofilm model

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    The aim of the study was to assess the impact of laser irradiation during antimicrobial photodynamic therapy. Test chambers containing each a salivary pellicle layer and a Stretococcus mutans culture were analyzed using confocal laser microscopy after adding a photosensitizer. Half of the chambers were irradiated with a diode laser. Comparing baseline fluorescence with the values after laser irradiation, a decrease of fluorescence could be observed. The non-irradiated group showed a slight increase of fluorescence. The present study indicates that laser irradiation is an essential part to reduce bacteria by antimicrobial photodynamic therapy.

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

    PubMed

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

    2011-05-01

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

  5. Target cell specific antibody-based photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    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).

  6. Interstitial photodynamic therapy in a rat liver metastasis model.

    PubMed Central

    van Hillegersberg, R.; Marijnissen, J. P.; Kort, W. J.; Zondervan, P. E.; Terpstra, O. T.; Star, W. M.

    1992-01-01

    Photodynamic therapy (PDT) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue. We therefore investigated interstitial tumour illumination as a means of selective PDT. A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats. Photofrin was administered (5 mg kg-1 i.v.) 2 days before laser illumination. Tumours with a mean (+/- s.e.) diameter of 5.7 +/- 0.1 mm (n = 106, 20 days after implantation) were illuminated with 625 nm light, at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100, 200, 400, 800 or 1600 J cm-1. Control groups received either laser illumination only, Photofrin only or diffuser insertion only. Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas. Long-term effects were studied on day 36. To determine the biochemistry of liver damage and function, serum ASAT and ALAT levels were measured on day 1 and 2, and antipyrine clearance on day 1. Tumour and surrounding liver necrosis increased with light dose delivered (P < 0.001). Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals. No deterioration in liver function was found. The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1457339

  7. Two-photon excitation photodynamic therapy with Photofrin

    NASA Astrophysics Data System (ADS)

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

    2005-09-01

    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.

  8. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  9. Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

    2005-01-01

    Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

  10. Galactodendritic Phthalocyanine Targets Carbohydrate-Binding Proteins Enhancing Photodynamic Therapy

    PubMed Central

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

    2014-01-01

    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

  11. Photodynamic therapy: a new antimicrobial approach to infectious disease?

    PubMed Central

    Hasan, Tayyaba

    2011-01-01

    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

  12. Manual and rotary instrumentation ability to reduce Enterococcus faecalis associated with photodynamic therapy in deciduous molars.

    PubMed

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

    2014-12-01

    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

  13. Novel adjuvant therapy for heat-assisted capsular shift procedures

    NASA Astrophysics Data System (ADS)

    Aksan, Alptekin; McGrath, John J.

    2001-06-01

    Heat-Assisted Capsular Shift (HACS) procedures are currently applied to treat shoulder (glenohumeral) instability. The therapy aims at thermally denaturing the collagenous framework, thus shrinking the surrounding soft tissues of the lax glenohumeral joint. The desired outcome of the therapy is restoring the kinematic stability of the joint without degrading its mechanical stability. Reports describing the outcome of HACS procedures reveal considerable variations, most likely due to utilization of different heat deposition modalities and the diversity of the thermal treatment protocols applied. The uncertainty of the outcome is also amplified by the post-heating recovery from shrinkage and the heat-induced degradation of mechanical stability. This study introduces a novel method designed to minimize the adverse effects of current therapies. A mechanical property enhancement technique in the form of an adjuvant chemical treatment is presented. In-vitro experiments performed on rabbit patellar tendons using a new arthroscopic fluid with thermal treatment indicate therapeutic improvement compared to therapies based on heating alone. A decrease in the strain recovery as large as 50% and an increase in stiffness as much as 100% have been produced in collagenous tissues without compromising strength. In summary, this work presents the initial results of an effort aimed at increasing the safety and reliability of currently applied HACS procedures by optimal manipulation of novel thermo-chemical treatments.

  14. Optical Dosimetry and Treatment Planning for Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Baran, Timothy M.

    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.

  15. Studies of photodynamic therapy: Investigation of physiological mechanisms and dosimetry

    NASA Astrophysics Data System (ADS)

    Woodhams, Josephine Helen

    Photodynamic therapy (PDT) is a treatment for a range of malignant and benign lesions using light activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen species (in particular singlet oxygen). Since the PDT cytotoxic effect depends on oxygen, monitoring of tissue oxygenation during PDT is important for understanding the basic physiological mechanisms and dosimetry of PDT. This thesis describes the use of non-invasive, optical techniques based on visible light reflectance spectroscopy for the measurement of oxy- to deoxyhaemoglobin ratio or haemoglobin oxygen saturation (HbSat). HbSat was monitored at tissue sites receiving different light dose during aluminium disulphonated phthalocyanine (AIS2PC) PDT. Results are presented on real time PDT-induced changes in HbSat in normal tissue (rat liver) and experimental tumours, and its correlation with the final biological effect under different light regimes, including fractionated light delivery. It was found to some extent that changes in HbSat could indicate whether the tissue would be necrotic after PDT and it was concluded that online physiological dosimetry is feasible for PDT. The evaluation of a new photosensitiser for PDT called palladium-bacteriopheophorbide (WST09) has been carried out in normal and tumour tissue in vivo. WST09 was found to exert a strong PDT effect but was active only shortly after administration. WST09 produced substantial necrosis in colonic tumours whilst only causing a small amount of damage to the normal colon under certain conditions indicating a degree of selectivity. Combination therapy with PDT for enhancing the extent of PDT-induced damage has been investigated in vivo by using the photochemical internalisation (PCI) technique and Type 1 mechanism enhanced phototoxicity with indole acetic acid (IAA). PCI of gelonin using AIS2PC PDT in vivo after systemic administration of gelonin was shown to enhance the effect of PDT in normal liver. The use of PDT and IAA did not result in a synergistic response.

  16. Adherence to adjuvant endocrine therapy for breast cancer: importance in women with low income.

    PubMed

    Ursem, Carling J; Bosworth, Hayden B; Shelby, Rebecca A; Hwang, Wenke; Anderson, Roger T; Kimmick, Gretchen G

    2015-05-01

    There are wide disparities in breast cancer-specific survival by patient sociodemographic characteristics. Women of lower income, for instance, have higher relapse and death rates from breast cancer. One possible contributing factor for this disparity is low use of adjuvant endocrine therapy-an extremely efficacious therapy in women with early stage, hormone receptor positive breast cancer, the most common subtype of breast cancer. Alone, adjuvant endocrine therapy decreases breast cancer recurrence by 50% and death by 30%. Data suggest that low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome in low-income breast cancer patients. PMID:25884292

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

    PubMed

    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

    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

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

    PubMed Central

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

    2009-01-01

    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

  19. Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

    PubMed Central

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

    2011-01-01

    Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource. PMID:21765637

  20. The Effect of Aminolevulinic Acid Photodynamic Therapy on Microcomedones and Macrocomedones

    Microsoft Academic Search

    G. Fabbrocini; S. Cacciapuoti; V. De Vita; N. Fardella; F. Pastore; G. Monfrecola

    2009-01-01

    Background: Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been shown to be an effective treatment for acne. However, the effect of ALA PDT on comedo formation has never been objectively evaluated. Cyanoacrylate follicular biopsy (CFB), a noninvasive procedure, has been proposed as the most reliable tool for studying follicular casts. Objective: To determine the possible effect of ALA and

  1. Topical ALA-Photodynamic Therapy for the Treatment of Acne Vulgaris

    Microsoft Academic Search

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

    2000-01-01

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

  2. Modulation of cellular Ca 2+-signaling during hypericin-induced photodynamic therapy (PDT)

    Microsoft Academic Search

    Gesine Pfaffel-Schubart; Angelika Rück; Claudia Scalfi-Happ

    2006-01-01

    During photodynamic therapy (PDT) the interaction between light and photosensitizers induces oxidative stress through the production of reactive oxygen species (ROS). The intracellular localization of the photosensitizer determines the signaling pathways started by its photoactivation. One of these pathways is modulated by changes in the local Ca2+-concentration, which may induce further reactions leading to cell stimulation or cell death.In this

  3. Photodynamic therapy to the oral cavity, tongue and larynx: a canine normal tissue tolerance study

    Microsoft Academic Search

    Merrill A. Biel; William Janssen; Michael F. Trump

    1995-01-01

    Photodynamic therapy (PDT) has the potential to treat early carcinomas of the oral cavity and larynx while preserving normal tissue. However, normal tissues retain the photosensitizing agents and may be activated by high light fluence and dose rates resulting in normal tissue necrosis. The effects of varying dose rates of light delivery on various tissues in the upper aerodigestive tract

  4. A novel medical robot assisting photodynamic therapy for port wine stains

    Microsoft Academic Search

    Gui-bin Bian; Xing-guang Duan; Qiang Huang; Xing-tao Wang; Shi-hu Cui; Naiyan Huang; Ying Gu

    2010-01-01

    Port wine stain (PWS) birthmarks are congenital vascular malformations, which usually appear at birth and tend to become darker and thicker with age's growth. Vasculartargeted photodynamic therapy (PDT) is an effective approach in the treatment of PWS. However, due to the arbitrariness of manual operation and pole points existing in laser radiation, the PWS zone was always cured unevenly in

  5. How we treat Bowen's disease with topical photodynamic therapy in Dundee.

    PubMed

    Attili, Sasi Kiran; Ibbotson, Sally H

    2009-03-01

    We have more than 10 years experience in the Photobiology Unit, in the use of topical photodynamic therapy (PDT) for non-melanoma skin cancer and other skin diseases. During this time we have undertaken approximately 5000 treatments and this article details the practical aspects of how we treat Bowen's disease with topical PDT. PMID:19447370

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

    Microsoft Academic Search

    Jason Luu; Keith Redmond; William Lo; Paul Chow; Lothar Lilge; Jonathan Rose

    2009-01-01

    Photodynamic therapy (PDT) is a method of treating cancer that combines light and light-sensitive drugs to selectively destroy cancerous tumours without harming the healthy tissue. The success of PDT depends on the accurate computation of light dose distribution. Monte Carlo (MC) simulations can provide an accurate solution for light dose distribution, but have high computation time that prevents them from

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

    Microsoft Academic Search

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

    2006-01-01

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

  8. Real-time optoacoustic monitoring of vascular damage during photodynamic therapy treatment of tumor

    Microsoft Academic Search

    Liangzhong Xiang; Da Xing; Huaimin Gu; Diwu Yang; Sihua Yang; Lvming Zeng; Wei R. Chen

    2007-01-01

    The optoacoustic technique is a noninvasive imaging method with high spatial resolution. It potentially can be used to monitor anatomical and physiological changes. Photodynamic therapy PDT-induced vascular damage is one of the important mechanisms of tumor destruction, and real-time monitoring of vascu- lar changes can have therapeutic signicance. A unique optoacoustic system is developed for neovascular imaging during tumor photo-

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

    PubMed

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

    2014-01-01

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

  10. Histological findings of surgically excised choroidal neovascular membranes after photodynamic therapy

    Microsoft Academic Search

    U E K Schnurrbusch; K Welt; L-C Horn; P Wiedemann; S Wolf

    2001-01-01

    AIMTo investigate effects of photodynamic therapy (PDT) on human choroidal neovascularisation (CNV).METHODSTwo patients with recurrences after PDT with verteporfin underwent surgical extraction of the CNV. Immediately after surgical excision the subfoveal neovascular membranes were divided for light microscopic and for electron microscopic processing. For light microscopy tissues were embedded in paraffin. Sections were stained with haematoxylin and eosin, and the

  11. Anastomotic Vessels Remain Viable after Photodynamic Therapy in Primate Models of Choroidal Neovascularization

    Microsoft Academic Search

    Mark H. Criswell; Thomas A. Ciulla; Lisa A. Lowseth; Ward Small; Ronald P. Danis; Dennis L. Carson

    PURPOSE. Anastomotic vessels in exudative age-related macular degeneration (AMD) represent a serious clinical feature that reportedly does not respond well to either photocoagulation or photodynamic therapy (PDT). Anastomoses also occur in various animal models of choroidal neovascularization (CNV). In the present study, anastomotic vessels and their patency were evaluated in two primate CNV laser-trauma models after PDT, by using two

  12. Fluorescence diagnosis and photodynamic therapy for lower genital tract diseases – A review

    Microsoft Academic Search

    Peter Hillemanns; Philipp Soergel; Martin Löning

    2009-01-01

    Fluorescence diagnosis (FD) and photodynamic therapy (PDT) are modern methods which are evaluated in different fields in gynecology. FD is under investigation as a method gynecological conditions such as cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), endometriosis and ovarian cancer. PDT is being evaluated in a multicentric randomized phase-II study for the treatment of human papillomavirus (HPV)-associated CIN using

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

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1992-06-01

    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.

  14. ALA and ALAester-mediated Photodynamic Therapy of Human Glioma Spheroids

    Microsoft Academic Search

    Henry Hirschberg; Chung-Ho Sun; Bruce J. Tromberg; Steen J. Madsen

    2002-01-01

    The effects of photodynamic therapy (PDT) in human glioma spheroids incubated in 5-aminolevulinic acid (ALA), or ALA esters, are investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations, light doses, and dose rates. The primary finding of this study is that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA

  15. Photodynamic Therapy of Skin Cancers: Sensitizers, Clinical Studies and Future Directives

    Microsoft Academic Search

    Fernanda S. De Rosa; M. Vitória L. B. Bentley

    2000-01-01

    Photodynamic therapy (PDT) is a new modality of skin cancer treatment. It involves the administration of photosensitizing drugs which, when localized in tumor tissue can produce its destruction by absorbing an adequate dose of light of an appropriate wavelength. A large number of photosensitizing agents have been tested in PDT experiments. Topical application of 5-aminolevulinic acid (5-ALA) followed by light

  16. Porphyrin synthesis from aminolevulinic acid esters in endothelial cells and its role in photodynamic therapy

    Microsoft Academic Search

    Lorena Rodriguez; Henriëtte S. de Bruijn; Gabriela Di Venosa; Leandro Mamone; Dominic J. Robinson; Angeles Juarranz; Alcira Batlle; Adriana Casas

    2009-01-01

    Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing microcirculatory shutdown. Protoporphyrin IX generated from 5-aminolevulinic acid (ALA) has been widely used as an endogenous photosensitiser in PDT. However, the hydrophilic nature of the ALA molecule limits its penetration through the stratum corneum of the skin and cell membranes and thus, ALA alkyl-esters have been

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

    Microsoft Academic Search

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

    2008-01-01

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

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

    E-print Network

    Cao, Wenwu

    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. Fluorescence effective in the treatment of intimal hyperplasia, which contributes to restenosis, by eradicating cells

  19. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Khaing Oo, Maung Kyaw

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

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

    NASA Astrophysics Data System (ADS)

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

    2004-06-01

    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.

  1. Photodynamic Therapy as Novel Treatment for Halitosis in Adolescents: A Case Series Study

    PubMed Central

    Lopes, Rubia Garcia; de Santi, Maria Eugenia Simões Onofre; Franco, Bruno Edin; Deana, Alessandro Melo; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Ferrari, Raquel Agnelli Mesquita; Bussadori, Sandra Kalil

    2014-01-01

    Introduction: Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% of cases and systemic in 10% of cases. The foul odor is caused mainly by volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light with and without the combination of chemical agents has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by the photosensitizing dye. The aim of the present case series study was to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using a sulfide meter (Halimeter®). Methods: Five adolescents aged 14 to 16 years were evaluated using a sulfide meter before and one hour after photodynamic therapy, which involved the use of methylene blue 0.005% on the middle third and posterior thirds of the dorsum of the tongue and nine points of laser irradiation in the red band (660 nm) with an energy dose of 9 J, power output of 100 mW and 90-seconds exposure time. Results: A 31.8% reduction in the concentration of volatile sulfur compounds was found in the comparison of the initial and final readings. The statistically significant reduction (p = 0.0091) led to an absence of halitosis following treatment (mean: 58.2 ppb). Conclusion: Photodynamic therapy seems to be effective on reduction the concentration of volatile sulfur compounds.Considering the positive effects of photodynamic therapy in this case series, further studies involving microbiological analyses should be conducted to allow comparisons of the results. PMID:25653814

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

    PubMed

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

    2013-01-01

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

  3. Hypericin-based photodynamic therapy: antitumor activity, accumulation potential, and induced cell death pathway

    NASA Astrophysics Data System (ADS)

    Luksiene, Zivile; Vaitkuviene, Aurelija

    2004-09-01

    In this study the main interest was focused on the to investigation the photodynamic efficacy of hypericin, three other photosensitizers and 5 aminolevulinic acid-induced protopofirin IX in their ability to block the growth of rather aggressive tumor - Ehrlich ascite carcinoma in mice as well as Reh cells in humans (B-leukemia). Hypericin was found to exhibit the highest phototoxicity and antitumor activity in treating Ehrlich ascite carcinoma. The different photosensitizers were ranked as follows: Hypericin > hematoporphyrin dimethyl ether > Photofrin II > meso-tetra (para-sulfophenyl)porphin > 5-aminolevulinic acid. The most important is that just after Hyp-based photodynamic therapy 75% of mice survived a 4 month-period, and no recurrence of tumor within this period was detected in 25% of the treated mice. The clear cut correlation observed between intracellular dye concentration in the tumor cells and efficiency of photodynamic therapy, supports the idea that the intracellular accumulation of the photosensitizer is one of the most important factors in determining the benefit of photodynamic therapy. Hence, the accumulation of the photosensitizer in the tumor cells should be considered as one of the prognostic factors for the determination of the therapeutic outcome. Eventually, one of the most significant result is that hypericin is effective photosensitizer for human B-leukemia cells and induces apoptosis after photosensitization.

  4. Photosensitizers and light sources for photodynamic therapy of the Bowen’s disease

    Microsoft Academic Search

    M. A. CalinA; A. Diaconeasa; D. Savastru; M. Tautan

    2011-01-01

    Bowen’s disease is a neoplastic skin disease, known as squamous cell carcinoma in situ. The treatment options for Bowen’s\\u000a disease are: cryotherapy, curettage, surgery, topical therapy and radiotherapy. In the past recent years, photodynamic therapy\\u000a was used as a new treatment method. The purpose of this paper is to summarize the results of clinical and research studies\\u000a with respect to

  5. Two-photon photodynamic therapy and its potential application to age related macular degenerations

    NASA Astrophysics Data System (ADS)

    Karotki, Aliaksandr; Khurana, Mamta; Bisland, Stuart K.; Moriyama, Eduardo H.; Simpson, E. Rand; Campbell, Melanie C. W.; Collins, Hazel; Anderson, Harry L.; Cramb, David T.; Wilson, Brian C.

    2007-02-01

    Photodynamic therapy (PDT) using verteporfin is widely used for treatment of age related macular degeneration (AMD). Due to non-perfect selectivity of the drug accumulation in the neovasculature some collateral damage to healthy tissue arises during the treatment. Damage to healthy structures in the eye is always a concern because of a high probability of reducing visual acuity. Two-photon (2-?) photodynamic therapy potentially offers much higher treatment selectivity than its one-photon (1-?) counterpart. By utilizing focused light for 2-? excitation, treatment volumes on the order of microliters can be achieved thus maximizing localized insult to abnormal blood vessels and sparing healthy tissue. We propose that 2-? photodynamic therapy will be valuable in the treatment of choroidal neovascularization secondary to age related macular degeneration as well as other conditions. To ascertain feasibility of 2-? photodynamic therapy we measured 2-? spectrum and cross sections of verteporfin (80 GM at 940 nm, 1 GM = 10 -50 cm 4s/photon), chlorin e6 (14 GM at 800 nm) and tetrasulfonated aluminum phthalocyanine (140 GM at 900 nm) and investigated their in vitro efficiency under 2-? excitation. Only verteporfin demonstrated cell kill under the used irradiation parameters (average light intensity 9.1 mW, wavelength 850 nm, total light dose 6900 J/cm2). Dorsal skinfold window chamber model in mouse was used to test efficiency of 2-? PDT with verteporfin in vivo. Although we were able to induce photodynamic damage to a blood vessel using 1-? excitation, 2-? excitation resulted in no visible damage to irradiated blood vessel. The most probable reason is low efficiency of verteporfin as a 2-? photosensitizer. We also report 2-? spectrum of new photosensitizer, HCC4 (4300 GM at 830 nm), specifically designed for efficient 2-? excitation.

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2012-01-01

    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

  8. Nanoscintillator Conjugates as Photodynamic Therapy-Based Radiosensitizers: Calculation of Required Physical Parameters

    PubMed Central

    Morgan, Nicole Y.; Kramer-Marek, Gabriela; Smith, Paul D.; Camphausen, Kevin; Capala, Jacek

    2011-01-01

    The recent demonstration of nanoscale scintillators has led to interest in the combination of radiation and photodynamic therapy. In this model, scintillating nanoparticles conjugated to photosensitizers and molecular targeting agents would enhance the targeting and improve the efficacy of radiotherapy and extend the application of photodynamic therapy to deeply seated tumors. In this study, we calculated the physical parameters required for these nanoparticle conjugates to deliver cytotoxic levels of singlet oxygen at therapeutic radiation doses, drawing on the published literature from several disparate fields. Although uncertainties remain, it appears that the light yield of the nanoscintillators, the efficiency of energy transfer to the photosensitizers, and the cellular uptake of the nano-particles all need to be fairly well optimized to observe a cytotoxic effect. Even so, the efficacy of the combination therapy will likely be restricted to X-ray energies below 300 keV, which limits the application to brachytherapy. PMID:19267550

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

    Microsoft Academic Search

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

    2003-01-01

    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.

  10. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

  11. Pleural Photodynamic Therapy and Surgery in Lung Cancer and Thymoma Patients with Pleural Spread

    PubMed Central

    Tseng, Ying-Fan; Shieh, Ming-Jium; Chen, Jin-Shing; Lai, Hong-Shiee; Lee, Jang-Ming

    2015-01-01

    Pleural spread is difficult to treat in malignancies, especially in lung cancer and thymoma. Monotherapy with surgery fails to have a better survival benefit than palliative chemotherapy, the currently accepted treatment. Photodynamic therapy utilizes a photosensitizer to target the tumor site, and the tumor is exposed to light after performing a pleurectomy and tumor resection. However, the benefits of this procedure to lung cancer or thymoma patients are unknown. We retrospectively reviewed the clinical characteristics and treatment outcomes of patients with lung cancer or thymoma with pleural seeding who underwent pleural photodynamic therapy and surgery between 2005 and 2013. Eighteen patients enrolled in this study. The mean patient age was 52.9 ± 12.2 years. Lung cancer was the inciting cancer of pleural dissemination in 10 patients (55.6%), and thymoma in 8 (44.4%). There was no procedure-related mortality. Using Kaplan-Meier survival analysis, the 3-year survival rate and the 5-year survival rate were 68.9% and 57.4%, respectively. We compared the PDT lung cancer patients with those receiving chemotherapy or target therapy (n = 51) and found that the PDT group had better survival than non-PDT patients (mean survival time: 39.0 versus 17.6 months; P = .047). With proper patient selection, radical surgical resection combined with intrapleural photodynamic therapy for pleural spread in patients with non-small cell lung cancer or thymoma is feasible and may provide a survival benefit. PMID:26193470

  12. Adjuvant therapy use among Appalachian breast cancer survivors.

    PubMed

    Tan, Xi; Marshall, Vincent D; Anderson, Roger T; Donohoe, Joseph; Camacho, Fabian; Balkrishnan, Rajesh

    2015-07-01

    There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival.A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline-recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) ?0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model.About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio?=?2.82, P?adjuvant treatment use. PMID:26131828

  13. Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal oral cancer therapies.

    PubMed

    Wang, Beike; Wang, Jia-Hong; Liu, Qian; Huang, Hao; Chen, Ming; Li, Kaiyang; Li, Chengzhang; Yu, Xue-Feng; Chu, Paul K

    2014-02-01

    Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient singlet oxygen generation when illuminated by 532 nm green light and high photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro experiments show that reactive oxygen species generated by green light and hyperthermia produced by NIR light constitute two different mechanisms for cancer cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing the uptake of RB by cancer cells. In vivo experiments are conducted on hamster cheek pouches to resemble the human oral cancer conditions more accurately to assess the therapeutic effectiveness. Compared to the single photodynamic therapy (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT capabilities provide better therapeutic effects against oral cancer and have large potential in cancer treatment. PMID:24331707

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent; Gustafson, Scott; Jacques, Steven

    2008-05-01

    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.

  16. Adjuvant Therapy in Renal Cell Carcinoma—Past, Present, and Future?

    PubMed Central

    Janowitz, Tobias; Welsh, Sarah J.; Zaki, Kamarul; Mulders, Peter; Eisen, Tim

    2013-01-01

    To date, no effective adjuvant treatment for renal cell carcinoma (RCC) has been described, but research in this area is important since the 5-year relapse rate for intermediate- and high-risk early-stage RCC is 30%–40%. Metastatic RCC can be treated successfully with immune therapy and targeted therapy. Adjuvant trials with immune therapy have been conducted, but they reported no benefit in disease-free survival, and clinical trials with targeted agents have not yet reported results. Further advances in our understanding of the molecular pathogenesis of RCC will identify additional potential targets for adjuvant treatment trials. Future challenges will consequently include target identification, as well as trial design to answer multiple trial questions concurrently, comprehensively, and economically. We review the past efforts, summarize the current adjuvant clinical trial landscape, and consider the challenges in adjuvant trials for RCC. Additionally, we identify potential future adjuvant trial treatments and propose an alternative design for future adjuvant clinical trials. PMID:23972712

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

    PubMed Central

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

    2015-01-01

    Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes. PMID:25821448

  18. Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes

    Microsoft Academic Search

    Ursula Schlötzer-Schrehardt; Arne Viestenz; Gottfried O. H. Naumann; Horst Laqua; S. Michels; Ursula Schmidt-Erfurth

    2002-01-01

    Purpose. To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes. Methods. One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration. Two laser spots and two light doses (50 J\\/cm2

  19. Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

    Microsoft Academic Search

    Baris Karakullukcu; Kim van Oudenaarde; Marcel P. Copper; W. M. C. Klop; Robert van Veen; Maarten Wildeman; I. Bing Tan

    2011-01-01

    The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason\\u000a is that the success rates are not well established. The current paper analyzes our institutional experience of early stage\\u000a oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary\\u000a or non-primary treatment

  20. Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers

    Microsoft Academic Search

    M. Wakui; Yoshihito Yokoyama; H. Wang; T. Shigeto; M. Futagami; H. Mizunuma

    2010-01-01

    Purpose  Photodynamic therapy (PDT) is a new approach to cancer treatment that utilizes photochemical reactions induced by a combination\\u000a of an oncophilic photosensitizing agent and laser light. With an aim to apply PDT for intraperitoneal disseminated foci of\\u000a advanced or recurrent ovarian cancers, the present study was conducted to evaluate the antitumor effect of PDT using a methyl\\u000a ester of 5-aminolevulinic

  1. Clinical trials of a new chlorin photosensitizer for photodynamic therapy of malignant tumors

    Microsoft Academic Search

    Valeriy A. Privalov; Alexander V. Lappa; Oleg V. Seliverstov; Alexey B. Faizrakhmanov; Nicolay N. Yarovoy; Elena V. Kochneva; Michail V. Evnevich; Alla S. Anikina; Andrey V. Reshetnicov; Igor D. Zalevsky; Yuriy V. Kemov

    2002-01-01

    Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and

  2. Fluorescence Resonance Energy Transfer Reveals a Binding Site of a Photosensitizer for Photodynamic Therapy1

    Microsoft Academic Search

    Rachel L. Morris; Kashif Azizuddin; Minh Lam; Jeffrey Berlin; Anna-Liisa Nieminen; Malcolm E. Kenney; Anna C. S. Samia; Clemens Burda; Nancy L. Oleinick

    Phthalocyanine (Pc) 4, like many photosensitizers for photodynamic therapy (PDT), localizes to intracellular membranes, especially mitochon- dria. Pc 4-PDT photodamages Bcl-2 and Bcl-xL, antiapoptotic proteins interacting with the permeability transition pore complex that forms at contact sites between the inner and outer mitochondrial membranes. These complexes and the inner membrane are unique in containing the phospholipid cardiolipin. Nonyl-acridine orange (NAO)

  3. The role of light-emitting diodes for photodynamic therapy of brain tumors

    Microsoft Academic Search

    Meic H. Schmidt; Dawn M. Bajic; Kenneth W. Reichert II; Glenn A. Meyer; Harry T. Whelan; Todd S. Martin

    1996-01-01

    The development of more effective light sources for Photodynamic Therapy (PDT) of brain tumors would be of benefit for both research and clinical application. In this study, the use of light-emitting diode arrays for PDT of brain tumors with Photofrin® porfimer sodium was investigated. An inflatable balloon device with an LED tip was constructed. These light-emitting diodes (LED’s) are based

  4. Antimicrobial effect of photodynamic therapy using a highly pure chlorin e6

    Microsoft Academic Search

    Jong-Hwan Park; Yeon-Hee Moon; Iel-Soo Bang; Yong-Chul Kim; Soo-A Kim; Sang-Gun Ahn; Jung-Hoon Yoon

    2010-01-01

    The aim of the present study is to evaluate the antimicrobial effect of photodynamic therapy (PDT) using a highly pure chlorin\\u000a e6 (Ce6), against various pathogenic bacteria. To examine the antimicrobial effect of Ce6-mediated PDT against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhimurium, inhibition zone formation, CFU quantification, and bacterial viability were evaluated. Inhibition zone\\u000a analysis

  5. Structural and functional effects of endometrial photodynamic therapy in a rat model

    Microsoft Academic Search

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

    1996-01-01

    OBJECTIVE: Our purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid. STUDY DESIGN: Three hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber. RESULTS: A 64 J\\/cm2 in situ optical dose resulted

  6. Erythrosine is a potential photosensitizer for the photodynamic therapy of oral plaque biofilms

    Microsoft Academic Search

    Simon Wood; Daniel Metcalf; Deirdre Devine; Colin Robinson

    2006-01-01

    Results: The CLSM results showed that erythrosine is taken up into S. mutans biofilms, where it is associated with the biomass of the biofilm rather than the fluid-filled channels and voids. Comparison of the cell killing efficacy of erythrosine in S. mutans biofilms of different ages showed that erythrosine was1-2log10moreeffectiveatkillingbiofilmbacteriathanphotofrinand0.5-1log10moreeffectivethanMB. The results were statistically significant (P < 0.01). Photodynamic therapy

  7. Enhancement of erythrosine-mediated photodynamic therapy of Streptococcus mutans biofilms by light fractionation

    Microsoft Academic Search

    Daniel Metcalf; Colin Robinson; Deirdre Devine; Simon Wood

    Objectives: We aimed to increase the bacterial cell killing efficacy of erythrosine-mediated photodynamic therapy (PDT) of Streptococcus mutans biofilms by fractionating the delivered light dose into a series of shorter pulses. Methods: S. mutans biofilms of 200 mm thickness were grown in a constant-depth film fermenter (CDFF). Biofilms were incubated with 22 mM erythrosine before being irradiated with white light

  8. Photodynamic therapy combined with posterior subtenon triamcinolone acetonide injection in the treatment of choroidal neovascularization

    Microsoft Academic Search

    Y-A Lee; T-C Ho; M-S Chen; C-H Yang; C-M Yang

    2009-01-01

    PurposeTo evaluate the therapeutic effect of photodynamic therapy (PDT) combined with posterior subtenon injection of triamcinolone acetonide (PSTA) in the treatment of choroidal neovascularization (CNV).MethodsIn this retrospective case–control study, treatment outcomes at 12 months of patients with CNV were reviewed. One hundred and two consecutive patients (102 eyes) with subfoveal CNV of various causes were included. Patients in the study

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

    Microsoft Academic Search

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

    2004-01-01

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

  10. Photodynamic therapy and intravitreal triamcinolone for extrafoveal choroidal neovascularization in neovascular age-related macular degeneration

    Microsoft Academic Search

    Jonathan Etter; Sharon Fekrat

    2006-01-01

    We report a case of extrafoveal choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration\\u000a treated with photodynamics therapy (PDT) and intravitreal triamcinolone. Nine months following PDT and intravitreal triamcinolone,\\u000a no ophthalmoscopic or angiographic evidence of recurrent CNV in the left eye was found. The intraocular pressure (IOP) increased\\u000a from 10 mmHg on presentation to 20 mmHg at 9 months.

  11. Diffuse choroidal haemangioma in Sturge–Weber syndrome treated with photodynamic therapy under general anaesthesia

    Microsoft Academic Search

    E. A. Huiskamp; R. P. H. M. Müskens; A. Ballast; J. M. M. Hooymans

    2005-01-01

    Purpose: To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment as sociated with diffuse choroidal haemangioma in Sturge-Weber syn- drome. Methods: An interventional case report of a 12-year-old girl with Sturge-Weber syndrome who devel- oped an exudative retinal detachment (visual acuity 20\\/400) that was treated with PDT under general anaesthesia. PDT was performed according

  12. Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

    Microsoft Academic Search

    Steen J. Madsen; Marlon S. Mathews; Even Angell-Petersen; Chung-Ho Sun; Van Vo; Rogelio Sanchez; Henry Hirschberg

    2009-01-01

    Photodynamic therapy (PDT) has been investigated as a postoperative treatment in patients with high grade gliomas. The purpose\\u000a of this in vitro investigation was to determine whether motexafin gadolinium (MGd), a known radiation sensitizer, could potentiate\\u000a the effects of 5-aminolevulinic acid (ALA)-PDT. Human glioma (ACBT) spheroids (250 ?m diameter) were incubated in 5-aminolevulinic\\u000a acid (ALA) with and without MGd and irradiated with

  13. Fractionated Illumination Significantly Improves the Response of Superficial Basal Cell Carcinoma to Aminolevulinic Acid Photodynamic Therapy

    Microsoft Academic Search

    Ellen R M de Haas; Bastiaan Kruijt; Henricus J C M Sterenborg; H A Martino Neumann; Dominic J Robinson

    2006-01-01

    Photodynamic therapy (PDT) of superficial basal cell carcinoma (sBCC) using topical 5-aminolevulinic acid (ALA) and a light fluence of 75–100 J cm?2 yields unsatisfactory long-term results. In several animal models, illumination with two light fractions 2 hours apart was considerably more effective than single illumination. Response is further enhanced if the fluence of the first light fraction is reduced, although

  14. Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study

    Microsoft Academic Search

    Eric P. Estey; Kevin Brown; Zhenjun Diwu; Jixiang Liu; J. William Lown; Gerald G. Miller; Ronald B. Moore; John Tulip; Malcolm S. McPhee

    1996-01-01

    Hypocrellin compounds were selected as potential photosensitizers for photodynamic therapy (PDT) owing to their high quantum\\u000a yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light\\u000a absorption in the red spectral region, among other properties. Parent hypocrellins A and B share an absorption peak at 658?nm.\\u000a These molecules may therefore be considered

  15. Scavengers Protection of Cells Against ALA-based Photodynamic Therapy-induced Damage

    Microsoft Academic Search

    C. Perotti; A. Casas; A. M. Del C. Batlle

    2002-01-01

    .\\u000a \\u000a The exogenously stimulated formation of intracellularly generated protoporphyrin IX, a precursor of haem, is becoming one\\u000a of the fastest developing areas in the field of photodynamic therapy (PDT). We tested the action of several free radical scavengers,\\u000a amino acids, antioxidants and sulphur-containing compounds as protectors from photodamage induced by 5-aminolaevulinic acid\\u000a (ALA)-mediated PDT, employing the LM2 cell line, derived

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

    PubMed Central

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

    2015-01-01

    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

  17. Susceptibility of planktonic cultures of Streptococcus mutans to photodynamic therapy with a light-emitting diode.

    PubMed

    Costa, Anna Carolina Borges Pereira A; Chibebe Junior, José; Pereira, Cristiane Aparecida; Machado, Ana Karina da Silva; Beltrame Junior, Milton; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2010-01-01

    The objective of this study was to evaluate the effect of photodynamic therapy with erythrosine and rose bengal using a light-emitting diode (LED) on planktonic cultures of S. mutans. Ten S. mutans strains, including nine clinical strains and one reference strain (ATCC 35688), were used. Suspensions containing 10? cells/mL were prepared for each strain and were tested under different experimental conditions: a) LED irradiation in the presence of rose bengal as a photosensitizer (RB+L+); b) LED irradiation in the presence of erythrosine as a photosensitizer (E+L+); c) LED irradiation only (P-L+); d) treatment with rose bengal only (RB+L-); e) treatment with erythrosine only (E+L-); and f) no LED irradiation or photosensitizer treatment, which served as a control group (P-L-). After treatment, the strains were seeded onto BHI agar for determination of the number of colony-forming units (CFU/mL). The results were submitted to analysis of variance and the Tukey test (p ? 0.05). The number of CFU/mL was significantly lower in the groups submitted to photodynamic therapy (RB+L+ and E+L+) compared to control (P-L-), with a reduction of 6.86 log?? in the RB+L+ group and of 5.16 log?? in the E+L+ group. Photodynamic therapy with rose bengal and erythrosine exerted an antimicrobial effect on all S. mutans strains studied. PMID:21180961

  18. Hypoxia Induced by Upconversion-Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors.

    PubMed

    Liu, Yanyan; Liu, Yong; Bu, Wenbo; Cheng, Chao; Zuo, Changjing; Xiao, Qingfeng; Sun, Yong; Ni, Dalong; Zhang, Chen; Liu, Jianan; Shi, Jianlin

    2015-07-01

    Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia. PMID:26012928

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

    PubMed Central

    HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

    2015-01-01

    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/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) 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). PMID:25546823

  20. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Z. X.; Huang, Y. Z.; Shi, S. G.; Tang, S. H.; Li, D. H.; Chen, X. L.

    2014-07-01

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

  1. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premaligant lesions: an in vivo study

    Microsoft Academic Search

    Yih-Chih Hsu; Chun-Pin Chiang; Jian Wen Chen; Ying-Ru Chen; Jeng-Woei Lee

    2010-01-01

    One of the best strategies to prevent the occurrence of oral cancer is to eliminate oral precancers and block their further malignant transformation. Previous studies showed that photosan-mediated photodynamic therapy (photosan-PDT) is very effective for human head and neck cancers. To avoid the systemic photodynamic toxicity of photosan, this study was designed to use a topical photosan-PDT for treatment of

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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

  3. Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical practice guideline

    Microsoft Academic Search

    Richard A Malthaner; Rebecca KS Wong; R Bryan Rumble; Lisa Zuraw

    2004-01-01

    BACKGROUND: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer. METHODS: A systematic review with meta-analysis was developed and clinical recommendations

  4. Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy

    Microsoft Academic Search

    Alan W. Partin; James L. Mohler; Steven Piantadosi; Charles B. Brendler; Martin G. Sanda; Patrick C. Walsh; Jonathan I. Epstein; Jonathan W. Simons; Fray F. Marshall

    1995-01-01

    ObjectivesFollowing surgery, men with recurrent prostate cancer have an isolated elevation in serum prostate-specific antigen (PSA) well in advance of measurable metastatic disease. Rational patient selection for new forms of adjuvant therapy, for example, gene therapy, is imperative.

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

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

    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.

  6. Suppression of neointimal hyperplasia by photodynamic therapy: in vitro and in vivo results

    NASA Astrophysics Data System (ADS)

    Sobeh, Mohammed S.; Chan, Philip; Greenwald, Stephen E.; Ham, Robert J.; Wood, Alan J.; Cross, Frank W.; Hsiang, York N.

    1994-07-01

    Proliferation of vascular smooth muscle cells (VSMCs) is the pathophysiogical basis of the restenoses which occur in 30-55% of patients undergone revascularisation. Prophylactic measures including pharmacotherapy, endovascular stenting and anti-gene therapy have so far failed to contain this problem. Photodynamic therapy (PDT) may selectively suppress VSMCs and decrease restenosis rates. We report 2 studies; the first examines the effect of PDT on an in-vitro model of NIH and the second involves using endoluminal ablation of an in-vivo model of experimental NIH of the rabbit's aorta.

  7. [Photodynamic therapy of a cholangiocarcinoma in an 80-year-old man].

    PubMed

    Ulstrup, Thomas; Pedersen, Finn Møller

    2013-02-25

    70% of cholangiocarcinomas (CC) are perihilar lesions. At the time of diagnosis few are candidates for complete resection, and the standard palliative therapy has been biliary stenting. Studies have shown that photodynamic therapy (PDT) improves survival time. In this case report we describe an 80-year-old man with rheumatoid arthritis and perihilar CC classified as Bismuth-Corlette type II who successfully underwent PDT as the first patient in Denmark. The treatment was well tolerated with no phototoxic skin reaction, and a subsequent endoscopic retrograde cholangiopancreatography showed reduction of tumour. PMID:23608010

  8. Photodynamic therapy of cerebral glioma - a review. Part II - clinical studies.

    PubMed

    Stylli, Stanley S; Kaye, Andrew H

    2006-08-01

    Photodynamic therapy (PDT) is a binary treatment modality that has been used to treat malignant brain tumours for 25 years. The treatment involves the selective uptake of a photosensitizer (PS) by the tumour cells followed by irradiation of the tumour with light of the appropriate wavelength to excite and activate the PS resulting in selective tumour destruction and is a potentially valuable adjunct to surgical excision and other conventional therapies. PDT has undergone extensive laboratory studies and clinical trials with a variety of PS and tumour models. These are discussed with reference mainly to clinical studies involving the PDT of brain tumours. PMID:16567094

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

    Microsoft Academic Search

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

    2000-01-01

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

  10. Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy

    PubMed Central

    Mfouo-Tynga, Ivan; Abrahamse, Heidi

    2015-01-01

    The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events. PMID:25955645

  11. Cell death pathways and phthalocyanine as an efficient agent for photodynamic cancer therapy.

    PubMed

    Mfouo-Tynga, Ivan; Abrahamse, Heidi

    2015-01-01

    The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events. PMID:25955645

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  14. Vaginal Speculum For Photodynamic Therapy And Method Of Using The Same

    DOEpatents

    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

    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.

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

    Microsoft Academic Search

    Zhimin Tong; Gurmit Singh; Andrew J. Rainbow

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

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

    PubMed

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

    2014-04-14

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

  17. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

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

    2011-08-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    SciTech Connect

    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

    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.

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

    NASA Astrophysics Data System (ADS)

    Menyaev, Yulian A.; Zharov, Vladimir P.

    2006-02-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

    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.

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

    PubMed

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  5. SU-E-T-191: First Principle Calculation of Quantum Yield in Photodynamic Therapy

    SciTech Connect

    Abolfath, R; Guo, F; Chen, Z; Nath, R [Yale New Haven Hospital, New Haven, CT (United States)

    2014-06-01

    Purpose: We present a first-principle method to calculate the spin transfer efficiency in oxygen induced by any photon fields especially in MeV energy range. The optical pumping is mediated through photosensitizers, e.g., porphyrin and/or ensemble of quantum dots. Methods: Under normal conditions, oxygen molecules are in the relatively non-reactive triplet state. In the presence of certain photosensitizer compounds such as porphyrins, electromagnetic radiation of specific wavelengths can excite oxygen to highly reactive singlet state. With selective uptake of photosensitizers by certain malignant cells, photon irradiation of phosensitized tumors can lead to selective killing of cancer cells. This is the basis of photodynamic therapy (PDT). Despite several attempts, PDT has not been clinically successful except in limited superficial cancers. Many parameters such as photon energy, conjugation with quantum dots etc. can be potentially combined with PDT in order to extend the role of PDT in cancer management. The key quantity for this optimization is the spin transfer efficiency in oxygen by any photon field. The first principle calculation model presented here, is an attempt to fill this need. We employ stochastic density matrix description of the quantum jumps and the rate equation methods in quantum optics based on Markov/Poisson processes and calculate time evolution of the population of the optically pumped singlet oxygen. Results: The results demonstrate the feasibility of our model in showing the dependence of the optical yield in generating spin-singlet oxygen on the experimental conditions. The adjustable variables can be tuned to maximize the population of the singlet oxygen hence the efficacy of the photodynamic therapy. Conclusion: The present model can be employed to fit and analyze the experimental data and possibly to assist researchers in optimizing the experimental conditions in photodynamic therapy.

  6. 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)

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

    1996-12-01

    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.

  7. A method for video-assisted thoracoscopic photodynamic therapy (VAT-PDT).

    PubMed

    Moghissi, Keyvan; Dixon, Kate; Thorpe, J Andrew C

    2003-09-01

    A technique is described for application of photodynamic therapy (PDT) to peripheral pulmonary and other intrathoracic malignant tumours. For video-assisted thoracoscopic-PDT we advocate the use of the flexible fibreoptic bronchoscope through an appropriately placed port. This, together with the standard thoracoscope and attached monitor can provide three-dimensional visualisation of the intrathoracic lesion and more importantly allow the accurate delivery of laser light to the tumour. At the present time we have successfully used this method without complication in three patients with advanced inoperable disease. PMID:17670074

  8. Long-term healing of photodynamic therapy: treatment of experimental intimal hyperplasia

    NASA Astrophysics Data System (ADS)

    LaMuraglia, Glenn M.; ChandraSekar, N. R.; Flotte, Thomas J.; Hasan, Tayyaba

    1994-07-01

    A study was performed to determine whether intimal hyperplasia can be chronically inhibited and the artery wall integrity maintained after cells are depleted from the artery with photodynamic therapy. Utilizing chloroaluminum sulfonated phthalocyanine or saline for control, limited balloon injury of the common carotid artery was performed before irradiation with 675 mm laser light. Results demonstrated carotid inhibition of intimal hyperplasia in PDT treated arteries without aneurysm formation or artery dilatation. By 4 weeks there was reendothelialization of the intima of the PDT arteries and repopulation of the adventitia with myofibroblasts. This data was encouraging in that PDT can chronically inhibit intimal hyperplasia without precipitating a weakness in the arterial wall.

  9. 808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  11. Photodynamic Therapy with Photofrin Reduces Invasiveness of Malignant Human Glioma Cells

    Microsoft Academic Search

    F. Jiang; M. Chopp; M. Katakowski; K. K. Cho; X. Yang; N. Hochbaum; L. Tong; T. Mikkelsen

    2002-01-01

    .\\u000a \\u000a In this study we investigated the influence of Photofrin-based photodynamic therapy (PDT) on the migration of two human glioma\\u000a cell lines in vitro. U87 and U25ln tumour cells were treated with Photofrin at various doses and subjected to a fixed optical\\u000a (632?nm) dose of 100?mJ\\/cm2. Photofrin cytotoxicity was determined using MTT and colony forming assays. Using a matrigel artificial

  12. Design of the optical phantom of tissue for photodynamic therapy research

    NASA Astrophysics Data System (ADS)

    Xie, Shusen; Profio, A. E.; Shu, Kuang-Hsien

    1993-03-01

    An optical phantom of tissue has been devised to simulate the optical properties of typical tissues for research in photodynamic therapy (PDT). The phantom consists of a scatterer (polystyrene-divinylbenzene microspheres) and an absorber (india ink) in distilled water. A set of relevant data for the microscopic optical properties and macroscopic optical parameter of the phantom was found. The results obtained approximate the optical properties of typical tissues. This optical phantom may duplicate the spatial variation of the radiant energy fluence of typical human tissues at 630 nm wavelength in PDT.

  13. Photodynamic therapy for multiple central type lung cancer - a case report.

    PubMed

    Takahashi, Eisuke; Koshiishi, Haruya; Sakaniwa, Nobuyuki; Okunaka, Tetsuya; Takei, Hidefumi; Hayashi, Naganobu; Takahashi, Masayoshi; Ikeda, Norihiko

    2014-11-01

    In case of central type lung cancer, it happens that tumors tend to grow at many foci of bronchial tree, sometimes simultaneously and sometimes not. And these patients with such abnormalities often suffer from pulmonary emphysema or chronic bronchitis because of heavy smoking habits. So it is important to choose the treatment which preserve the pulmonary function in these cases. Today among several kinds of treatments, photodynamic therapy (PDT) is the definite method to maintain lung function. We report here a case of multiple central type lung cancer treated successfully by PDT. PMID:25731416

  14. Cross-Resistance to Cisplatin in Cells Resistant to Photofrin-mediated Photodynamic Therapy

    Microsoft Academic Search

    Roger A. Moorehead; Steven G. Armstrong; Brian C. Wilson; Gurmit Singh

    2008-01-01

    This study shows that a Photofrmn-induced photodynamic therapy resistant variant (RIF-SA) of a radiation-induced flbrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diammlnedlchloroplatinum(ll) (cisplatin). This is the first study to show cross-resistanceto cisplatin in photody namictherapy-resistant variantsin vitro.Resistance doesnotappeartobe theresultof elevatedglutathione levelssinceneithertheresistantvariant (RIF-8A) nor the parental line (RIF-l) varied in total glutathione levels. However,cisplatin-DNA adductlevelsdifferedsignificantly betweenthe two cell types. Immediately following

  15. Endoscopic Photodynamic Therapy: Fiber Optic Delivery For The Treatment Of Esophageal And Bronchial Cancer

    NASA Astrophysics Data System (ADS)

    Mang, Thomas S.; Nava, Hector R.; Regal, Anne-Marie

    1989-06-01

    Clinical studies in photodynamic therapy (PDT) have utilized lasers to take advantage of coupling efficiencies to optical fibers allowing light to be delivered to many areas of the body. This is particularly true in endoscopic PDT. Both interstitial and superficial delivery techniques can be applied using one of a variety of delivery fibers available. A fiber with an optically flat end with a lens to produce a spot with a homogeneous intensity is used for superficial applications. Diffusers of various lengths, at the tip of a fiber, produce a cylindrical isotropic pattern and are suited for either intraluminal or interstitial illuminations.

  16. Chorioretinal anastomosis and photodynamic therapy:a two-year follow-up study

    Microsoft Academic Search

    Rufino M. Silva; M. Luz Cachulo; João Figueira; José R. Faria de Abreu; J. G. Cunha-Vaz

    2007-01-01

    Background  To evaluate the two-year efficacy of photodynamic therapy with Visudyne (PDT) in neovascular age-related macular degeneration\\u000a (AMD) eyes with chorioretinal anastomosis (CRA).\\u000a \\u000a \\u000a \\u000a Methods  A non-randomized, institutional, prospective study, of 28 consecutive eyes of 23 patients, with CRA, treated with PDT. Masked\\u000a best corrected visual acuity (VA) and angiographic features at baseline and during the period of two years were evaluated.\\u000a \\u000a \\u000a \\u000a Results  Twenty

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

    Microsoft Academic Search

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

    2006-01-01

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

  18. Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

    Microsoft Academic Search

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

    2008-01-01

    Purpose  To study contrast-enhanced MRI guided photodynamic therapy with a pegylated bifunctional polymer conjugate containing an MRI\\u000a contrast agent and a photosensitizer for minimally invasive image-guided cancer treatment.\\u000a \\u000a \\u000a \\u000a 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\\u000a and tumor targeting was non-invasively visualized in

  19. Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

    PubMed

    Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

    2010-12-01

    A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area. PMID:21140993

  20. Intracellular antimicrobial photodynamic therapy: a novel technique for efficient eradication of pathogenic bacteria.

    PubMed

    Nakonechny, Faina; Firer, Michael A; Nitzan, Yeshayahu; Nisnevitch, Marina

    2010-01-01

    The increasing resistance of bacteria to antibiotics is a serious problem, caused in part by excessive and improper use of these drugs. One alternative to traditional antibiotic therapy is photodynamic antimicrobial chemotherapy (PACT) which is based on the use of a photosensitizer (PS), activated by illumination with visible light. The poor penetration of visible light through the skin limits the application of PACT to the treatment of skin infections or the use of invasive procedures. To overcome this problem we report the exploitation of light emitted as a result of the chemiluminescent reaction of luminol to excite the PS and we call this process chemiluminescent photodynamic antimicrobial therapy (CPAT). We studied the effect of free and liposome-encapsulated PS (methylene blue or toluidine blue) on bacteria under excitation by either white external light or chemiluminescence emitted by free or liposome-enclosed luminol. PACT showed slightly better performance that CPAT for free and encapsulated PS for both types of bacteria. CPAT resulted in a three log suppression of Staphylococcus aureus and two log suppression of Escherichia coli growth. The use of CPAT may prove to be a novel and more effective form of antimicrobial therapy, particularly for internal infections not easily accessible to traditional PACT. PMID:20880227

  1. New distributors for homogeneous and monitorable light delivery in photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1995-01-01

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

  2. Results of adjuvant therapy in resected pancreatic cancer

    Microsoft Academic Search

    Åke Andrén-Sandberg; Pia Lena Biiekman; Roland Andersson

    1997-01-01

    Summary  After an apparently curative resection, most patients develop local recurrence within the resection bed. In addition, almost\\u000a all develop liver metastases. This implies that the surgical resection, even if extended, seldom is enough, and that an adjuvant\\u000a treatment must be effective not only against systemic spread, but also against local recurrence. However, the time schedule\\u000a may be different for different

  3. Improved adjuvant endocrine therapy for premenopausal women with endocrine responsive disease

    PubMed Central

    Goldhirsch, Aron; Colleoni, Marco; Regan, Meredith

    2015-01-01

    Results from two randomised global trials (SOFT & TEXT) designed to newly define the most effective components of adjuvant endocrine therapy for premenopausal women with endocrine responsive disease, showed that for some, those with high risk of relapse, the use of the aromatase inhibitor exemestane together with ovarian function suppression with GnRH analogue (triptorelin) yielded the most favourable treatment outcome compared with tamoxifen. For women with low risk of relapse, treatment with tamoxifen was similar to ovarian function suppression together with either exemestane or tamoxifen. For women with intermediate risk of relapse, ovarian function suppression added to tamoxifen was not inferior to exemestane, while it resulted in superior outcomes compared to tamoxifen alone. Now, these trials provide critical information for the adjuvant treatment of premenopausal women with endocrine responsive breast cancer and are important for the development of future trials for further improvement of adjuvant endocrine therapies for the younger population.

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

    PubMed

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

    2014-12-23

    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

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

    PubMed

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

    2015-03-24

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

  6. [Physical treatment methods for acne. Light, laser, photodynamic therapy and peeling].

    PubMed

    Borelli, C; Korting, H C

    2010-02-01

    The medical treatment of acne is generally sufficient to meet the expectations of acne patients. However, in a number of situations additional therapeutic approaches may be advisable. There are a wide variety of useful physical methods. They range from electromagnetic waves, usually light, to peeling and manual therapy. Phototherapy of acne includes not just visible light but also laser and flash lamp therapy. The present review provides an overview on the evidence. Visible light, in particular blue light, provides an effective option for treatment of inflammatory acne. Photodynamic therapy also is efficacious; however, it should not be used because of an unfavorable risk-benefit ratio. UV treatment of acne is obsolete. Newer studies on the use of a variety of laser systems and flash lamps have demonstrated in part rewarding results. PMID:20107751

  7. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; ?iplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  8. Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: Where do we stand?

    PubMed Central

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

    2014-01-01

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

  9. Merkel cell carcinoma adjuvant therapy: Current data support radiation but not chemotherapy

    Microsoft Academic Search

    Kelly M. Garneski; Paul Nghiem

    Merkel cell carcinoma (MCC) is a skin cancer with 30% mortality and an incidence that has tripled in the past 15 years. There is agreement that surgical excision with negative margins is an appropriate therapeutic first step and that sentinel lymph node biopsy is a powerful prognostic indicator. After excision of detectable cancer, optimal adjuvant therapy is not well established.

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

    Microsoft Academic Search

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

    2010-01-01

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

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

    SciTech Connect

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

    2012-02-01

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

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

    SciTech Connect

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

    2008-03-01

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

  13. Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: current and future evidence.

    PubMed

    Blok, E J; Derks, M G M; van der Hoeven, J J M; van de Velde, C J H; Kroep, J R

    2015-03-01

    The optimal duration and regimen of adjuvant hormonal therapy for premenopausal and postmenopausal patients with hormone receptor positive early breast cancer has not yet been established. This review will give an overview of published and ongoing studies concerning extended endocrine treatment. Most of the currently published studies are based on the adjuvant treatment regime of 5 years tamoxifen, which has been proven to be inferior compared to aromatase inhibitor (AI)-containing regimes. Therefore, until today, there is no clear evidence for the extension of endocrine therapy after upfront AI-based adjuvant treatment regimes. Multiple clinical trials, which will be discussed in this review, are ongoing to elucidate on this matter. We emphasize the need for tailoring of extended adjuvant endocrine treatment. The quest for predictive biomarkers, which are currently being investigated in the context of decision-making whether or not to start adjuvant chemotherapy, should be expanded to include the feasibility of extended endocrine treatment based on these markers. By tailoring the extension of endocrine treatment, overtreatment, side effects and unnecessary costs will be prevented. PMID:25698635

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

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

    PubMed

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

    2015-04-01

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

  16. Enhancement of protoporphyrin IX performance in aqueous solutions for photodynamic therapy.

    PubMed

    Homayoni, Homa; Jiang, Ke; Zou, Xiaoju; Hossu, Marius; Rashidi, Leila Hossein; Chen, Wei

    2015-06-01

    Molecular modification of protoporphyrin IX (PpIX) was conducted to improve its water solubility and therapeutic performance for photodynamic therapy. The carboxylic acid and the two nitrogen atoms in the core of PpIX molecule were protonated following by conjugation with 3-aminopropyl triethoxysilane (APTES). Then, folic acid (FA) was conjugated to the APTES-coated PpIX (MPpIX) through chemical bonding between FA and protonated PpIX. The results showed that APTES coating can stabilize PpIX and increase its water solubility. Consequently, this leads to the enhancement in luminescence and singlet oxygen production. Upon X-ray irradiation, singlet oxygen can be detected in the MPpIX but not in PpIX. This means that MPpIX can be used for deep cancer treatment as X-ray can penetrate deeply into tissue. Molecular modification also reduces the dark toxicity of PPIX and increases their cell uptake. All these traits indicate that the Molecular modification of PpIX may potentially improve the efficacy of photodynamic therapy for cancer treatment. PMID:25636780

  17. Non-coherent light for photodynamic therapy of superficial tumours in animals.

    PubMed

    Reeds, K B; Ridgway, T D; Higbee, R G; Lucroy, M D

    2004-09-01

    Cultured 9L cells were incubated with varying concentrations of pheophorbide-a-hexyl ether (HPPH) and then exposed to 665-nm red light from a non-coherent light source or a dye laser. Cell death was produced by both light sources, with the non-coherent light being most effective at the highest HPPH concentrations. To assess the feasibility of using the non-coherent light source for clinical photodynamic therapy (PDT), four dogs and three cats presenting with spontaneous superficial tumours were injected intravenously with 0.15 mg kg(-1) of HPPH, 1 h before their tumours were irradiated with 665-nm non-coherent light (50 mW cm(-2), 100 J cm(-2)). Of the nine tumours treated, there were eight complete responses, all occurring in animals with squamous cell carcinoma. After 68 weeks of follow-up, the median initial disease-free interval had not been reached. These data suggest that non-coherent light sources may be efficacious for photodynamic therapy of spontaneous superficial tumours in animals, representing a cost-effective alternative to medical lasers in both veterinary and human oncology. PMID:19379303

  18. 808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    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

    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

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

    PubMed Central

    2015-01-01

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

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

    PubMed Central

    Inguscio, Valentina; Panzarini, Elisa; Dini, Luciana

    2012-01-01

    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

  2. Assessment of cellular damage by comet assay after photodynamic therapy in vitro.

    PubMed

    Macecek, Jaroslav; Kolárová, Hana; Psotová, Jitka; Bajgar, Robert; Huf, Martin; Nevrelová, Pavla; Tomeeka, Marek; Mosinger, Jirí

    2004-01-01

    The aim of this study was analysis of DNA damage in the cell line of the human melanoma G361 after photodynamic therapy (PDT) by comet assay. Photodynamic therapy is based on cytotoxic action of sensitizers (10 microM ZnTPPS4 fixed into 1 mM cyclodextrin hpbetaCD) and light with a suitable wavelength. Single-cell gel electrophoresis (SCGE, comet assay) is a rapid and sensitive method for detecting DNA strand breaks at the level of single cells. Great amount of DNA damage was detected with the dose of irradiation of 0.1; 0.5 J and 2.5 J x cm(-2). Only radiation dose of visible light in the presence of sensitizers can induce DNA breaks of tumour cells. Cells with DNA damage appear as fluorescent comets with tails of DNA fragmentation. In contrast, cells with undamage DNA appear as round spots, because their intact DNA does not migrate out of the cell. PMID:15841921

  3. Combined chemotherapy and photodynamic therapy using a nanohybrid based on layered double hydroxides to conquer cisplatin resistance.

    PubMed

    Wang, Zhigang; Ma, Rong; Yan, Li; Chen, Xianfeng; Zhu, Guangyu

    2015-07-25

    A nanohybrid is assembled by ratiometrically co-loading Pt(iv) prodrugs and photosensitizers into layered double hydroxide nanoparticles. The nanohybrid shows synergistic cell-killing effects and is significantly active against the proliferation of cisplatin-resistant human cancer cells with nanomolar IC50 values. Profound mechanistic investigations confirm its action mode of combined chemo- and photodynamic therapy. PMID:26096645

  4. Is photodynamic therapy an appropriate treatment of feline superficial squamous cell carcinomas? Two case studies in small animal practice

    Microsoft Academic Search

    Elke Vinck; B. Cagnie; H. Vinck; D. Cambier

    2003-01-01

    Oncological research and cancer treatment are more common in human medicine than in veterinary medicine. Nevertheless the latest decennium chemotherapy, radiotherapy and surgery also figure largely in the cancer treatment of pets. For this matter, the present study tried to explore the applicability of Photodynamic Therapy (PDT) as a proper and advantageous alternative for those treatments. PDT using topical 5-aminolaevulinic

  5. Mode of action of photodynamic therapy with sulfonated aluminum phthalocyanine in induced squamous cell carcinomas in animal models

    Microsoft Academic Search

    W. Glafß; M. Káler; T. Lang

    1992-01-01

    In order to investigate the mechanism of action of photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AISPc) in squamous cell carcinoma, animal experiments were performed in induced carcinomas of the mucosa of the hamster's cheek pouch and skin of the laboratory mouse. Histological examinations revealed signs of massive interstitial bleeding, indicating a vascular response to PDT with AISPc. It was

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

    Microsoft Academic Search

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

    1990-01-01

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

  7. A Preliminary Study on the Prevention of Posterior Capsule Opacification by Photodynamic Therapy with Bacteriochlorin A in Rabbits

    Microsoft Academic Search

    Yasmine van Tenten; Hans J. Schuitmaker; Veva De Groot; Ben Willekens; Gijs F. J. M. Vrensen; Marie-José Tassignon

    2002-01-01

    Purpose: Photodynamic therapy (PDT) with bacteriochlorin a (BCA) has proven to be successful in the treatment of cancers and to be cytocidal for lens epithelial cells (LECs) in culture. The present study aimed to determine whether PDT with BCA is also effective in destroying LECs in the capsular bag in vivo and could therefore be a strategy for prevention of

  8. Preparation of fluorescent mesoporous hollow silica-fullerene nanoparticles via selective etching for combined chemotherapy and photodynamic therapy.

    PubMed

    Yang, Yannan; Yu, Meihua; Song, Hao; Wang, Yue; Yu, Chengzhong

    2015-07-28

    Well-dispersed mesoporous hollow silica-fullerene nanoparticles with particle sizes of ?50 nm have been successfully prepared by incorporating fullerene molecules into the silica framework followed by a selective etching method. The fabricated fluorescent silica-fullerene composite with high porosity demonstrates excellent performance in combined chemo/photodynamic therapy. PMID:26041655

  9. Role of Interleukin 1 and Granulocyte Colony-Stimulating Factor in Photofrin based Photodynamic Therapy of Rat Rhabdomyosarcoma Tumors1

    Microsoft Academic Search

    Wil J. A. de Vree; Maria C. Essers; Johan F. Koster

    1997-01-01

    Neutrophils play an important role in the efficacy of photodynamic therapy (PDT). These leukocytes rapidly accumulate into the tumor lesion after PDT and most likely eradicate the remaining attenuated tumor cells. The underlyingmechanismof the accumulationof neutrophilsat the time of PDT is not known. Therefore,we determinedthe effect of PDT on the course of mature and immature neutrophils in the circulation of

  10. Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy.

    PubMed

    Bhana, Saheel; Lin, Gan; Wang, Lijia; Starring, Hunter; Mishra, Sanjay R; Liu, Gang; Huang, Xiaohua

    2015-06-01

    We present the synthesis and application of a new type of dual magnetic and plasmonic nanostructures for magnetic-field-guided drug delivery and combined photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold nanopopcorns containing a self-assembled iron oxide cluster core were prepared via a seed-mediated growth method. The hybrid nanostructures are superparamagnetic and show great photothermal conversion efficiency (? = 61%) under near-infrared irradiation. Compact and stable nanocomplexes for photothermal-photodynamic therapy were formed by coating the nanoparticles with near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. The nanocomplex showed enhanced release and cellular uptake of the photosensitizer with the use of a gradient magnetic field. In vitro studies using two different cell lines showed that the dual mode photothermal and photodynamic therapy with the assistance of magnetic-field-guided drug delivery dramatically improved the therapeutic efficacy of cancer cells as compared to the combination treatment without using a magnetic field and the two treatments alone. The "three-in-one" nanocomplex has the potential to carry therapeutic agents deep into a tumor through magnetic manipulation and to completely eradicate tumors by subsequent photothermal and photodynamic therapies without systemic toxicity. PMID:25965727

  11. Long-term results after photodynamic therapy with verteporfin for choroidal neovascularizations secondary to inflammatory chorioretinal diseases

    Microsoft Academic Search

    Joachim Wachtlin; Heinrich Heimann; Tim Behme; Michael H. Foerster

    2003-01-01

    Background To evaluate the safety and the long-term effect on visual acuity of photodynamic therapy (PDT) for sub- and juxtafoveal choroidal neovascularizations (CNV) secondary to inflammatory conditions. Methods In a prospective pilot study, 19 patients with CNV due to inflammatory conditions underwent PDT treatment with verteporfin with standard parameters. Regular follow-up was carried out every 3 months with ETDRS visual

  12. Combined photodynamic therapy and intravitreal triamcinolone for the treatment of myopic choroidal neovascularization in a 13-year-old girl

    Microsoft Academic Search

    Michael J. Potter; Shelagh M. Szabo; Terrence Ho

    2006-01-01

    Background  Combination photodynamic therapy with verteporfin (PDT) and intravitreal triamcinolone acetonide (IVT) is currently being investigated as a treatment for choroidal neovascularization (CNV) due to age-related macular degeneration. However, PDT with triamcinolone has never previously been described in the treatment of CNV secondary to pathologic myopia, or in a young person. We describe the case of a young girl treated with

  13. Enhancement of 5-aminolevulinic-acid-induced photodynamic therapy using light-dose fractionation and iron-chelating agents

    Microsoft Academic Search

    Alison Curnow; Matthew J. Postle-Hacon; Alexander J. MacRobert; Stephen G. Bown

    1998-01-01

    Preliminary clinical studies of 5-aminolaevulinic acid (ALA) induced photodynamic therapy (PDT) with the maximum tolerated oral dose (60 mg\\/kg), currently appear to only produce limited amounts of necrosis. We have studied ways of increasing this effect without increasing the drug dose. In normal, female, Wistar rats we have found it possible to increase the area of necrosis produced in the

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

    PubMed

    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

    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

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

    NASA Astrophysics Data System (ADS)

    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

    2014-08-01

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

  16. Photodynamic therapy-induced angiogenic signaling: consequences and solutions to improve therapeutic response

    PubMed Central

    Gallagher-Colombo, Shannon M.; Maas, Amanda L.; Yuan, Min; Busch, Theresa M.

    2015-01-01

    Photodynamic therapy (PDT) can be a highly effective treatment for diseases ranging from actinic keratosis to cancer. While use of this therapy shows great promise in preclinical and clinical studies, understanding the molecular consequences of PDT is critical to designing better treatment protocols. A number of publications have documented alteration in angiogenic factors and growth factor receptors following PDT, which could abrogate treatment effect by inducing angiogenesis and re-establishment of the tumor vasculature. In response to these findings, work over the past decade has examined the efficacy of combining PDT with molecular targeting drugs, such as anti-angiogenic compounds, in an effort to combat these PDT-induced molecular changes. These combinatorial approaches increase rates of apoptosis, impair pro-tumorigenic signaling, and enhance tumor response. This report will examine the current understanding of PDT-induced angiogenic signaling and address molecular-based approaches to abrogate this signaling or its consequences thereby enhancing PDT efficacy.

  17. Successful treatment of cutaneous sarcoid by photodynamic therapy with minimal discomfort using a fractionated dosing regime.

    PubMed

    Patterson, Clare

    2009-10-01

    We report the case of a 42-year-old lady with an 8-year history of a persistent tumid plaque on her forehead. Investigations and presentation were consistent with cutaneous sarcoid with no systemic involvement. Multiple topical and oral treatments had been ineffective. She received seven sessions of 5-aminolaevulinic acid photodynamic therapy (PDT) over the course of 16 months. Each treatment was delivered in discontinuous and fractionated time intervals. Improvement was seen after the first treatment and continued with subsequent treatments. She found the treatment almost painless and was pleased with the cosmetic outcome. We conclude that PDT is a useful therapy in the treatment of facial cutaneous sarcoid. Fractionated exposure may allow the treatment to be less painful and therefore better tolerated. PMID:19747248

  18. Lanthanide-doped upconversion nanoparticles electrostatically coupled with photosensitizers for near-infrared-triggered photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Chen, Zhuo; Zheng, Wei; Zhu, Haomiao; Lu, Shan; Ma, En; Tu, Datao; Zhou, Shanyong; Huang, Mingdong; Chen, Xueyuan

    2014-06-01

    Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a ?-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy.Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a ?-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy. Electronic supplementary information (ESI) available: Tables S1 and S2 and Fig. S1-S13. See DOI: 10.1039/c4nr01826e

  19. Safety of adjuvant endocrine therapies in hormone receptor–positive early breast cancer

    PubMed Central

    Sehdev, S.; Martin, G.; Sideris, L.; Lam, W.; Brisson, S.

    2009-01-01

    Postmenopausal patients with hormone-sensitive early breast cancer are typically treated with adjuvant endocrine therapy, which significantly reduces the risk of recurrence. Because treatment is of a long duration, side effects from adjuvant therapy can be problematic. The aromatase inhibitors (AIS) are replacing tamoxifen as first-line treatment agents for early breast cancer. Here, we present the side-effect data associated with AIS in relation to bone, gynecologic, and cardiovascular health and to arthralgia and myalgia. Although AIS have been shown to decrease bone density, increase arthralgia, and affect vaginal health, these adverse events are usually manageable, and several strategies can be followed to improve quality of life in women on AI treatment. To optimize adherence to therapy. It is important that these issues are addressed so that women can benefit from treatment. PMID:19672417

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

    PubMed Central

    Engel, Jessica M.; Stankowski, Rachel V.

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25540662

  2. Phototherapy, photodynamic therapy and photophoresis in the treatment of connective-tissue diseases: a review.

    PubMed

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

    2015-07-01

    Connective-tissue disorders, which include lupus erythematosus, morphoea/scleroderma and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy (PDT) and photopheresis, are routinely utilized in the treatment of dermatological 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, PDT and photopheresis in the treatment of lupus erythematosus, morphoea/scleroderma and dermatomyositis. A MEDLINE search was conducted to find articles that discuss treatment of connective-tissue diseases with light therapies and more than 30 publications that discuss light therapy for these diseases were identified. These range 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 includes phototherapy, PDT 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, morphoea/scleroderma and dermatomyositis. PMID:25400115

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1994-07-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

    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.

  8. Fiber optic probes for tissue illumination in photodynamic diagnosis and therapy

    NASA Astrophysics Data System (ADS)

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

    1992-08-01

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

  9. Photodynamic therapy of spontaneous cancers in felines, canines, and snakes with chloro-aluminum sulfonated phthalocyanine.

    PubMed

    Roberts, W G; Klein, M K; Loomis, M; Weldy, S; Berns, M W

    1991-01-01

    This is the first report on the photodynamic treatment with a second-generation sensitizer, chloro-aluminum sulfonated phthalocyanine (CASPc) of spontaneously arising tumors and on the photodynamic therapy (PDT) of snake neoplasms. Each of 10 cats, 2 dogs, and 3 snakes presenting with a variety of tumor types (squamous cell carcinoma, mast cell malignant tumor, and mixed carcinoma/sarcoma) was given an intravenous injection of 1 mg of CASPc per kilogram body weight 48 hours prior to irradiation with 675-nm light. Some larger tumors (greater than 1.5 cm deep) were surgically debulked prior to PDT. No significant systemic toxicity or skin photosensitization was observed in any animal. The tumor responses were comparable to those seen with conventional cryotherapy, hyperthermia, or surgery. PDT with CASPc of these cases led to 67% (12 of 18) complete response, 22% (4 of 18) partial response, and 11% (2 of 18) no response (less than 50% reduction in tumor size). Four cases could not be evaluated. Since the overall tumor response to CASPc is very good, and the problem of skin photosensitivity is nonexistent, it is expected that using CASPc-PDT to eradicate human tumors would also yield comparable results. Further studies with long-term follow-up are necessary to optimize the use of CASPc-PDT in veterinary and human medicine. PMID:1824598

  10. Protein modified upconversion nanoparticles for imaging-guided combined photothermal and photodynamic therapy.

    PubMed

    Chen, Qian; Wang, Chao; Cheng, Liang; He, Weiwei; Cheng, Zhengping; Liu, Zhuang

    2014-03-01

    In this work, we develop a multifunctional nano-platform by coating upconversion nanoparticles (UCNPs) with bovine serum albumin (BSA), obtaining UCNP@BSA nanoparticles with great solubility and stability in physiological environments. Two types of dye molecules, including a photosensitizer, Rose Bengal (RB), and an NIR-absorbing dye, IR825, can be simultaneously loaded into the BSA layer of the UCNP@BSA nanoparticles. In this carefully designed UCNP@BSA-RB&; IR825 system, RB absorbs green light emitted from UCNPs under 980-nm excitation to induce photodynamic cancer cell killing, while IR825 whose absorbance shows no overlap with upconversion excitation and emission wavelengths, offers nanoparticles a strong photothermal perform under 808-nm laser irradiation. Without showing noticeable dark toxicity, the obtained dual-dye loaded nanoparticles are able to kill cancer via combined photothermal and photodynamic therapies, both of which are induced by NIR light with high tissue penetration, by a synergetic manner both in vitro and in vivo. In addition, the intrinsic paramagnetic and optical properties of Gd(3+)-doped UCNPs can further be utilized for in vivo dual modal imaging. Our study suggests that UCNPs with well-designed surface engineering could serve as a multifunctional nano-platform promising in cancer theranostics. PMID:24412081

  11. Antitumor effect of sinoporphyrin sodium-mediated photodynamic therapy on human esophageal cancer Eca-109 cells.

    PubMed

    Hu, Jianmin; Wang, Xiaobing; Liu, Quanhong; Zhang, Kun; Xiong, Wenli; Xu, Chuanshan; Wang, Pan; Leung, Albert Wingnang

    2014-01-01

    The aim of this study was to evaluate the photodynamic effect of Sinoporphyrin sodium (DVDMS). In this study, Eca-109 cells were treated with DVDMS (5 ?g mL(-1)) and subjected to photodynamic therapy (PDT). The uptake and subcellular localization of DVDMS were monitored by flow cytometry and confocal microscopy. The phototoxicity of DVDMS was studied by MTT assay. The morphological changes were observed by scanning electron microscopy (SEM). DNA damage, reactive oxygen species (ROS) generation and mitochondria membrane potential (MMP) changes were analyzed by flow cytometry. Studies demonstrated maximal uptake of DVDMS occurred within 3 h, with a mitochondrial subcellular localization. MTT assays displayed that DVDMS could be effectively activated by light and the phototoxicity was much higher than photofrin under the same conditions. In addition, SEM observation indicated that cells were seriously damaged after PDT treatment. Furthermore, activation of DVDMS resulted in significant increases in ROS production. The generated ROS played an important role in the phototoxicity of DVDMS. DVDMS-mediated PDT (DVDMS-PDT) also induced DNA damage and MMP loss. It is demonstrated that DVDMS-mediated PDT is an effective approach on cell proliferation inhibition of Eca-109 cells. PMID:25142812

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

    PubMed

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

    2008-06-01

    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

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

    PubMed

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

    2014-05-15

    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

  14. Anti-tumor immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

    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.

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

    PubMed

    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

    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

  16. 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

    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

    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

  17. LASER BIOLOGY AND MEDICINE: A laser-spectroscopy system for fluorescent diagnostics and photodynamic therapy of diseases of eye retina and choroid

    NASA Astrophysics Data System (ADS)

    Meerovich, G. A.; Shevchik, S. A.; Loshchenov, M. V.; Budzinskaya, M. V.; Ermakova, N. A.; Kharnas, S. S.

    2002-11-01

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

  18. Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

    PubMed Central

    van Oudenaarde, Kim; Copper, Marcel P.; Klop, W. M. C.; van Veen, Robert; Wildeman, Maarten; Bing Tan, I.

    2010-01-01

    The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results. PMID:20706842

  19. Monomeric pheophorbide(a)-containing poly(ethyleneglycol-b-epsilon-caprolactone) micelles for photodynamic therapy.

    PubMed

    Knop, Katrin; Mingotaud, Anne-Françoise; El-Akra, Naram; Violleau, Frédéric; Souchard, Jean-Pierre

    2009-03-01

    Incorporation of unaggregated monomeric molecules of pheophorbide(a) into micelles of poly(ethyleneoxide-b-epsilon-caprolactone) has been characterized by fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy and asymmetric flow field flow fractionation. It was shown that the method used leads to 20 nm micelles, corresponding to approximately 200 molecules of polymer and 4 molecules of monomeric pheophorbide(a) per nano-object which was able to generate (1)O(2) in the medium. They have been used thereafter as nanocarriers for photosensitizers in photodynamic therapy against cancer cells. The encapsulation of photosensitizer has been verified and in vitro tests on human cancerous cells have revealed a ca. 2-fold enhanced photocytotoxicity and cellular uptake compared to free pheophorbide(a). PMID:19255682

  20. Aminolevulinic acid hydrochloride with photodynamic therapy: efficacy outcomes and recurrence 4 years after treatment.

    PubMed

    Fowler, Joseph F; Zax, Robert H

    2002-06-01

    The safety and efficacy of treating individuals who presented with multiple actinic keratosis (AK) lesions with 5-aminolevulinic acid (ALA) in combination with photodynamic therapy (PDT) were documented in a phase III trial. This report highlights results of this phase III trial and reviews 4 specific cases of sustained AK lesion clearance 4 years after treatment with ALA/PDT Long-term recurrence data were collected from patients who participated in clinical trials of ALA/PDT Long-term evaluation extended to 36 to 48 months (4 years) supports primary efficacy findings of the phase III pivotal trial, with a low incidence of AK recurrence in patients treated with ALA/PDT PMID:12095067

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

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

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

  2. A Chlorin-Based Nanoscale Metal-Organic Framework for Photodynamic Therapy of Colon Cancers.

    PubMed

    Lu, Kuangda; He, Chunbai; Lin, Wenbin

    2015-06-24

    We report here the rational design of the first chlorin-based nanoscale metal-organic framework (NMOF), DBC-UiO, with much improved photophysical properties over the previously reported porphyrin-based NMOF, DBP-UiO. Reduction of the DBP ligands in DBP-UiO to the DBC ligands in DBC-UiO led to a 13 nm red shift and an 11-fold increase in the extinction coefficient of the lowest-energy Q band. While inheriting the crystallinity, stability, porosity, and nanoplate morphology of DBP-UiO, DBC-UiO sensitizes more efficient (1)O2 generation and exhibits significantly enhanced photodynamic therapy (PDT) efficacy on two colon cancer mouse models as a result of its improved photophysical properties. Both apoptosis and immunogenic cell death contributed to killing of cancer cells in DBC-UiO-induced PDT. PMID:26068094

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  4. Photodynamic therapy as a new approach in vulvovaginal candidiasis in murine model

    NASA Astrophysics Data System (ADS)

    Santi, Maria E.; Lopes, Rubia G.; Prates, Renato A.; Sousa, Aline; Ferreira, Luis R.; Fernandes, Adjaci U.; Bussadori, Sandra K.; Deana, Alessandro M.

    2015-02-01

    Vulvovaginal candidiasis is a common cause of vaginal infections. This study investigates the efficiency of antimicrobial photodynamic therapy (aPDT) against yeast cells in mice. Methylene blue (MB), malachite green (MG), and a special designed protoporphirin (PpNetNI) were used as photosensitizers. Female BALB-c mice were infected with Candida albicans ATCC 90028. PDT was applied with two different light sources, intravaginal and transabdominal. Vaginal washes were performed and cultivated for microbial quantification. Antimicrobial PDT was able to decrease microbial content with MB and PpNetNI (p<0.05), it was not effective, however, with MG photosensitizer. The results of this study demonstrate that aPDT may be a viable alternative treatment for vaginal candidiasis.

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

    PubMed Central

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

    2014-01-01

    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

  6. Dual-modal imaging and photodynamic therapy using upconversion nanoparticles for tumor cells.

    PubMed

    Yang, Chunna; Liu, Qiuling; He, Dacheng; Na, Na; Zhao, Yunling; Ouyang, Jin

    2014-12-21

    Here we synthesized silica-coated NaYF4:Yb,Tm@NaGdF4 nanoparticles with hypocrellin photosensitizers covalently incorporated inside the silica shells, combining dual modal imaging and photodynamic therapy (PDT) functions together. Under excitation at 980 nm, the tumor-targeting specificity of the as-prepared nanomaterials efficiently enhanced as folic acid (FA) was conjugated. The internalization of UCNPs@SiO2@hypocrellin A-FA in HeLa cells and HEK-293 cells was observed by confocal microscopy and in vitro magnetic resonance imaging (MRI), which demonstrated that the as-prepared nanocomposites have the ability to target folate receptor (FR) (+) cells. Moreover, magnetic resonance (MR) measurements also demonstrated that the as-prepared nanocomposites could be used as a contrast agent for MRI. All these results showed the feasibility and potential of the as-prepared nanocomposites for simultaneous imaging and PDT application. PMID:25327945

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

    PubMed

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

    2013-05-10

    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

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

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

    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.

  9. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

    PubMed Central

    Ericson, Marica B; Wennberg, Ann-Marie; Larkö, Olle

    2008-01-01

    The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field. PMID:18728698

  10. Photodynamic therapy for diffuse choroidal hemangioma in sturge-weber syndrome.

    PubMed

    Monteiro, Sílvia; Casal, Inês; Santos, Marinho; Meireles, Angelina

    2014-01-01

    Purpose. To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment (RD) associated with diffuse choroidal hemangioma in Sturge-Weber syndrome (SWS). Methods. An interventional case report of a 10-year-old girl with SWS who developed an exudative RD (visual acuity hand motions) that was treated with PDT. She was treated with a first session of multispot PDT. Posteriorly, a choroidotomy for drainage of subretinal fluid was created, combined with an intravitreal injection of gas (SF6) and cryoapplication. Finally, a second session of PDT was applied. Results. Subretinal fluid resolved over a period of one year and visual acuity increased to 20/125. Conclusions. PDT is an effective therapeutic option for exudative RD associated with diffuse choroidal hemangioma. PMID:24955093

  11. Photodynamic Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome

    PubMed Central

    Monteiro, Sílvia; Casal, Inês; Santos, Marinho

    2014-01-01

    Purpose. To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment (RD) associated with diffuse choroidal hemangioma in Sturge-Weber syndrome (SWS). Methods. An interventional case report of a 10-year-old girl with SWS who developed an exudative RD (visual acuity hand motions) that was treated with PDT. She was treated with a first session of multispot PDT. Posteriorly, a choroidotomy for drainage of subretinal fluid was created, combined with an intravitreal injection of gas (SF6) and cryoapplication. Finally, a second session of PDT was applied. Results. Subretinal fluid resolved over a period of one year and visual acuity increased to 20/125. Conclusions. PDT is an effective therapeutic option for exudative RD associated with diffuse choroidal hemangioma. PMID:24955093

  12. Study of light fluence rate distribution in photodynamic therapy using finite-element method

    PubMed Central

    Li, Jun; Zhu, Timothy C.; Finlay, Jarod C.

    2015-01-01

    In photodynamic therapy (PDT), it is desirable to determine the light fluence distribution accurately for treatment planning. Earlier studies have shown heterogeneous distribution of optical properties in patients’ prostates. Finiteelement method (FEM) is suitable for dealing with heterogeneous media and irregular geometries. Cylindrical diffusing fibers (CDFs) were modeled as linear sources of finite lengths, using the same parameters as those used in the treatments. Meshes were generated in the three-dimensional (3D) prostate geometry, reconstructed using transrectal ultrasound images of the prostate. Heterogeneous optical properties measured in the prostate were applied in the calculation and the refractive-index mismatch boundary condition was studied. Compared with the measurements, the FEM calculations using heterogeneous optical properties show better agreements than those using homogeneous optical properties.

  13. Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model.

    PubMed

    Bhuvaneswari, Ramaswamy; Ng, Qin Feng; Thong, Patricia S P; Soo, Khee-Chee

    2015-05-30

    Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab. PMID:25918252

  14. Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy.

    PubMed

    Çak?r, Dilek; Göksel, Meltem; Çak?r, Volkan; Durmu?, Mahmut; Biyiklioglu, Zekeriya; Kantekin, Halit

    2015-05-12

    Peripherally and non-peripherally tetra-substituted zinc(ii) phthalocyanines bearing 2-(2-{2-[3-(dimethylamino)phenoxy]ethoxy}ethoxy)ethoxy and 2-(2-{2-[3-(diethylamino)phenoxy]ethoxy}ethoxy)ethoxy groups (, , and ) were synthesized by cyclotetramerization of the corresponding phthalonitriles (, , and ). Their quaternized ionic derivatives (, , and ) were also synthesized by the reaction of them with methyl iodide. The novel compounds were characterized by using standard spectroscopic techniques such as FT-IR, (1)H NMR, (13)C NMR, UV-vis, mass and elemental analyses. The obtained quaternized phthalocyanines (, , and ) showed amphiphilic behaviour with excellent solubility in both organic and aqueous solutions, which makes them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel phthalocyanines were studied in DMSO for both non-ionic and ionic quaternized derivatives. However, these properties were examined in both DMSO and phosphate buffer solution (PBS) for quaternized ionic phthalocyanines. The effects of the positions of substituents (peripheral or non-peripheral) and the quaternization of the nitrogen atoms on the substituents about their photophysical and photochemical properties were also compared in this study. The bovine serum albumin (BSA) binding behaviours of the studied quaternized ionic zinc(ii) phthalocyanines were also described in PBS solutions. The quaternized phthalocyanines (, , and ) successfully displayed light-dependent photodamage in HeLa and HuH-7 cancer cells in photodynamic therapy treatment. The photosensitivity and the intensity of damage were found directly related to the concentration of the photosensitizers. PMID:25923925

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

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Grimland, Jennifer L.

    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.

  17. Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

    PubMed Central

    Gil, M; Bieniasz, M; Seshadri, M; Fisher, D; Ciesielski, M J; Chen, Y; Pandey, R K; Kozbor, D

    2011-01-01

    Background: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice. Methods: The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay. Results: Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue. Conclusion: These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV. PMID:21989183

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    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.

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

    PubMed Central

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

    2007-01-01

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

  20. Treatment of Upper Tract Urothelial Carcinoma: A Review of Surgical and Adjuvant Therapy

    PubMed Central

    Latchamsetty, Kalyan C; Porter, Christopher R

    2006-01-01

    Upper tract urothelial carcinoma is a disease entity that has not been as extensively studied and reviewed as carcinoma of the bladder. Recent advances in technology and adjuvant therapy have changed the treatment armamentarium of oncologists and urologists. A literature review was conducted that focused on newer surgical techniques, including laparoscopy and endoscopic management of upper tract disease. Adjuvant therapy including immunotherapy, chemotherapy, and radiation is also reviewed. Nephroureterectomy with removal of a bladder cuff still remains the gold standard of treatment. However, laparoscopic nephroureterectomy is quickly becoming popular, with equivalent recurrence rates. Because of the relatively recent introduction of laparoscopy into the urologic field, long-term data with respect to recurrence rates and survival rates are not yet available. Immunotherapy has also shown promise, but with higher recurrence rates than surgery. Chemotherapy and radiation also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Endoscopic management is acceptable in patients with severe medical comorbidities or solitary kidneys but requires rigorous and close follow-up. Adjuvant therapy with either chemotherapy or radiation is still debated but does offer some improvement in disease-specific survival. Randomized, prospective, placebo-controlled studies are required but are difficult to perform because of the relatively low incidence and prevalence of this disease. PMID:17021628

  1. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  2. Photodynamic Therapy

    MedlinePLUS

    ... treated skin will likely turn red and may swell after treatment. This usually peaks about a day ... will likely turn red and may blister and swell after treatment. Burning and stinging are common. The ...

  3. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    SciTech Connect

    Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Foote, Matthew C. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia) [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Diamantina Institute, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Elizabeth [Nursing Practice Development Unit, Princess Alexandra Hospital, Brisbane (Australia) [Nursing Practice Development Unit, Princess Alexandra Hospital, Brisbane (Australia); Research Centre for Clinical and Community Practice, Griffith University, Brisbane (Australia); Thomas, Janine [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia)] [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Meakin, Janelle [Clinical Trials Research Unit, Princess Alexandra Hospital, Brisbane (Australia)] [Clinical Trials Research Unit, Princess Alexandra Hospital, Brisbane (Australia); Smithers, B. Mark [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia) [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Bryan H. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia) [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia)

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  4. Adjuvant TNF-? therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness

    PubMed Central

    Cemazar, Maja; Todorovic, Vesna; Scancar, Janez; Lampreht, Ursa; Stimac, Monika; Kamensek, Urska; Kranjc, Simona; Coer, Andrej; Sersa, Gregor

    2015-01-01

    Background Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor ? (TNF-?) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods In vivo study was designed to evaluate the effect of TNF-? applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-? on electrochemotherapy with different cisplatin doses. Results A synergistic interaction between TNF-? and electrochemotherapy was observed. Administration of TNF-? before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-? administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-? induced blood vessel damage and increased tumour necrosis after combination of TNF-? and electrochemotherapy, indicating an anti-vascular action of TNF-?. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion Adjuvant intratumoural TNF-? therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective. PMID:25810699

  5. 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

    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

    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

  6. Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer

    PubMed Central

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

    2009-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    Kopelman, Raoul

    2008-03-01

    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.

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

    PubMed Central

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

    2014-01-01

    Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment. PMID:25364655

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

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1996-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Tibetan Medicated-Bath Therapy may Improve Adjuvant Arthritis in Rat.

    PubMed

    Chen, Huayue; Shoumura, Shizuko; Emura, Shoichi; Isono, Hideo

    2009-06-01

    Tibetan medicated-bath therapy has been applied to patients with rheumatoid arthritis for centuries. However, the detailed action mechanism of Tibetan medicated-bath therapy on the morphology and function of joints remains unknown. We designed our investigation to evaluate the efficacy of Tibetan medicated-bath therapy on adjuvant arthritis (AA) of rats in comparison with water-bath and dexamethasone administration. AA was induced by intradermal injection of Mycobacterium butyricum suspended in sterile mineral oil. The control animals were similarly injected with sterile vehicle. Eight days after injection, rats were treated with fresh-water bath, Tibetan medicated-bath (40 degrees C, 15 min) or intramuscular injection with dexamethasone for 21 consecutive days after which we evaluated the severity of arthritis visually and microscopically and measured serum interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels. While arthritis did not significantly change after water-bath treatment, the Tibetan medicated-bath and dexamethasone groups showed diminished joint swelling and alleviation of, inflammatory cell infiltration and the destruction of bone and cartilage. Serum IL-6 and TNF-alpha levels significantly decreased. Our results demonstrated that Tibetan medicated-bath therapy exerted a reliable effect on rat adjuvant arthritis, which may be involved in the inflammatory cytokines, IL-6 and TNF-alpha. Our data provide evidence for clinical use of Tibetan-medicated bath therapy for arthritis patients. PMID:18955278

  12. Tibetan Medicated-Bath Therapy may Improve Adjuvant Arthritis in Rat

    PubMed Central

    Shoumura, Shizuko; Emura, Shoichi; Isono, Hideo

    2009-01-01

    Tibetan medicated-bath therapy has been applied to patients with rheumatoid arthritis for centuries. However, the detailed action mechanism of Tibetan medicated-bath therapy on the morphology and function of joints remains unknown. We designed our investigation to evaluate the efficacy of Tibetan medicated-bath therapy on adjuvant arthritis (AA) of rats in comparison with water-bath and dexamethasone administration. AA was induced by intradermal injection of Mycobacterium butyricum suspended in sterile mineral oil. The control animals were similarly injected with sterile vehicle. Eight days after injection, rats were treated with fresh-water bath, Tibetan medicated-bath (40°C, 15 min) or intramuscular injection with dexamethasone for 21 consecutive days after which we evaluated the severity of arthritis visually and microscopically and measured serum interleukin (IL)-6 and tumor necrosis factor (TNF)-? levels. While arthritis did not significantly change after water-bath treatment, the Tibetan medicated-bath and dexamethasone groups showed diminished joint swelling and alleviation of, inflammatory cell infiltration and the destruction of bone and cartilage. Serum IL-6 and TNF-? levels significantly decreased. Our results demonstrated that Tibetan medicated-bath therapy exerted a reliable effect on rat adjuvant arthritis, which may be involved in the inflammatory cytokines, IL-6 and TNF-?. Our data provide evidence for clinical use of Tibetan-medicated bath therapy for arthritis patients. PMID:18955278

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

    PubMed Central

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

    2015-01-01

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

  14. Photodynamic application in neurosurgery: present and future

    Microsoft Academic Search

    Herwig Kostron

    2009-01-01

    Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence guided tumor resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as adjunctive treatment for malignant brain tumours. This review provides an overview on the current clinical data and trials as well as on photosensitisers, technical developments and indications for photodynamic application in Neurosurgery. Furthermore new developments and clinical

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

    PubMed Central

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

    2011-01-01

    The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT. PMID:16040251

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

    NASA Astrophysics Data System (ADS)

    Shrestha, Annie; Kishen, Anil

    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.

  17. Preliminary study of verteporfin photodynamic therapy in a canine prostate model

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  18. Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

    PubMed

    Yu, Jiashing; Hsu, Che-Hao; Huang, Chih-Chia; Chang, Po-Yang

    2015-01-14

    Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development. PMID:25494339

  19. Photodynamic therapy and the treatment of neoplastic diseases of the larynx, oral cavity, pharynx, and tracheobronchial tree

    Microsoft Academic Search

    Merrill A. Biel

    1993-01-01

    Photodynamic therapy has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Thirty patients with neoplasia of the head and neck have been treated with PDT with follow-up to twenty nine months. Four patients with T3 and T4 carcinomas of the upper aerodigestive tract had a partial response. Eleven patients with T1

  20. Photodynamic therapy and the treatment of neoplastic diseases of the larynx, pharynx, oral cavity, and tracheobronchial tree

    Microsoft Academic Search

    Merrill A. Biel

    1994-01-01

    Photodynamic therapy (PDT) has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Fifty-three patients with neoplasia of the head and neck have been treated with PDT with follow-up to 40 months. Eight patients with T2-T4 carcinomas of the upper aerodigestive tract had a partial response. Eighteen patients with CIS and T1

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

    SciTech Connect

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

    2009-01-01

    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.

  2. Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels

    Microsoft Academic Search

    Kanae Ichikawa; Tomoya Hikita; Noriyuki Maeda; Sei Yonezawa; Yoshito Takeuchi; Tomohiro Asai; Yukihiro Namba; Naoto Oku

    2005-01-01

    For the improvement of therapeutic efficacy in photodynamic therapy (PDT) by using a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), we previously prepared polyethylene glycol (PEG)-modified liposomes encapsulating BPD-MA (PEG-Lip BPD-MA). PEGylation of liposomes enhanced the accumulation of BPD-MA in tumor tissue at 3 h after injection of it into Meth-A-sarcoma-bearing mice, but, unexpectedly, decreased the suitability of the drug

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

    PubMed

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

    2014-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  5. Functionalising the azobenzene motif delivers a light-responsive membrane-interactive compound with the potential for photodynamic therapy applications.

    PubMed

    Hester, Theodore J; Dennison, Sarah R; Baker, Matthew J; Snape, Timothy J

    2015-08-01

    When adorned with n-octyl chains azobenzene is able to disrupt a variety of calcein-loaded phospholipid liposomes. The levels of lysis observed are dependent both on the lipid headgroup and the conformation of the azobenzene compound. In all cases studied, it has been shown that the cis-conformer is more membrane-interactive than the trans-conformer, suggesting that this class of molecule could be optimised for photo-dynamic therapy applications against infectious pathogens. PMID:26134592

  6. Photofrin-mediated Photodynamic Therapy Induces Vascular Occlusion and Apoptosis in a Human Sarcoma Xenograft Model1

    Microsoft Academic Search

    Brett W. Engbrecht; Chandrakala Menon; Alexander V. Kachur; Stephen M. Hahn; Douglas L. Fraker

    Photodynamic therapy (PDT) involves light activation of a photosensi- tizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the efficacy of PDT in treating human sarcomas, despite an ongoing clinical trial treating i.p. sarcomatosis. The present study evaluates PDT treatment of a human sarcoma xenograft in nude mice and explores the mechanism of PDT-mediated antitumor effect. Athymic

  7. In Vitro Photodynamic Therapy with Chlorin e6 Leads to Apoptosis of Human Vascular Smooth Muscle Cells

    Microsoft Academic Search

    Magdalena Wawrzy?ska; Wojciech Ka?as; Dariusz Bia?y; Ewa Zio?o; Jacek Arkowski; Walentyna Mazurek; Leon Strz?da?a

    2010-01-01

    Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However,\\u000a the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as\\u000a a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated\\u000a in vitro using human vascular smooth

  8. Dynamics of Retinal Function after Multiple Photodynamic Therapies in Age-Related Macular Degeneration: A Report of Cases

    Microsoft Academic Search

    Beatrix Feigl; Brian Brown; Jan Lovie-Kitchin; Lawrence Lee

    2005-01-01

    Purpose: To monitor retinal function after multiple laser treatments by photodynamic therapy (PDT) with the multifocal electroretinogram\\u000a (mfERG) in age-related macular degeneration (AMD). Methods: Five eyes of five subjects with AMD were investigated before the first and 1 month after each of three PDT treatments. Function\\u000a was assessed using the cone- and rod-mediated mfERG, high-contrast distance visual acuity, central visual fields

  9. A Trial of Short Incubation, Broad-Area Photodynamic Therapy for Facial Actinic Keratoses and Diffuse Photodamage

    Microsoft Academic Search

    Dany Touma; Mina Yaar; Sara Whitehead; Nellie Konnikov; Barbara A. Gilchrest

    Background: There is no completely satisfactory treat- ment for multiple actinic keratoses (AKs). Objective: To evaluate the efficacy of short incuba- tion, broad-area application of-aminolevulinic acid fol- lowed by exposure to activating light-photodynamic therapy (-ALA\\/PDT) for treatment of AKs and back- ground photodamage. The benefit of pretreatment with 40% urea cream to enhance penetration and the use of topical 3%

  10. Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents

    Microsoft Academic Search

    A Curnow; BW Mcllroy; MJ Postle-Hacon; JB Porter; AJ MacRobert; SG Bown

    1998-01-01

    Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum tolerated oral ALA dose (60 mg kg(-1)). This study investigates whether hydroxypyridinone iron-chelating agents can be used to enhance the tissue levels of PPIX, without increasing the administered dose of ALA. Quantitative charge-coupled device (CCD) fluorescence microscopy was employed to

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

    NASA Astrophysics Data System (ADS)

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

    2005-09-01

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

  12. Doctors' participation in randomized trials of adjuvant systemic therapy in breast cancer: how does it relate to their recommendations for standard therapy in breast cancer?

    Microsoft Academic Search

    P. M. Ellis; P. N. Buttow; R. J. Simes; M. H. N. Tattersall; S. M. Dunn; C. Macleod

    1999-01-01

    A cross-sectional survey of all medical and radiation oncologists in Australia was undertaken, plus surgeons listed as participants of the ANZ Breast Cancer Trials Group, to examine whether doctors' participation in randomized trials of adjuvant systemic therapy for breast cancer, is associated with their recommendations for adjuvant therapy in two clinical scenarios. Two-hundred and sixty-nine questionnaires were returned (response rate

  13. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    PubMed Central

    García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

    2014-01-01

    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

  14. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy.

    PubMed

    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-06-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = -2.6626 to -0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels. PMID:24756915

  15. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

    PubMed Central

    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-01-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = ?2.6626 to ?0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels. PMID:24756915

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

    PubMed Central

    Hayashi, Maiko; Fukuhara, Hideo; Inoue, Keiji; Shuin, Taro; Hagiya, Yuichiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects. PMID:25822972

  17. Highly water-soluble and tumor-targeted photosensitizers for photodynamic therapy.

    PubMed

    Li, Yuxi; Wang, Jin; Zhang, Xiaoxiao; Guo, Wenjun; Li, Fu; Yu, Min; Kong, Xiuqi; Wu, Wenjie; Hong, Zhangyong

    2015-07-01

    Biological uses of photosensitizers in photodynamic therapy (PDT) often suffer from a lack of tumor selectivity; a strategy based on molecule-targeted cancer therapies could provide a promising solution. To synthesize new water-soluble phthalocyanines (Pcs) for bio-conjugation with peptides or antibodies, we developed a method to synthesize asymmetrically substituted Pcs with both high water solubility and one monoamino group for conjugation with biological agents for tumor homing, using folic acid as the ligand model to direct the modified Pcs into target cells. Here, we report studies on the syntheses and characterization of these Pcs. In vitro and in vivo assays prove that the high solubility characteristic can greatly increase the tumor targeting capability of Pcs by reducing non-specific uptake. This newly designed photosensitizer accumulated almost completely in tumor regions, with a negligible signal found in other tissues in the xenograft tumor model. These initial data provide strong evidence of the high specificity tumor targeting of Pcs with folate and tri-glycerol substitutions. Theoretically, the synthesized Pcs could be conveniently conjugated to many other ligands, endorsing the broad applicability of this method for tumor-targeted PDT. PMID:26082999

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

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    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

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

    PubMed

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

    2014-09-01

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

  20. Role of Toll-like receptors in photodynamic-therapy-elicited host response

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    2004-07-01

    Treatment of solid tumors by photodynamic therapy (PDT) induces a host reaction, coordinated through a network of inflammatory and immune responses, that plays an important role in the therapy outcome. It is suggested that this host response is initiated by altered self-associated endogenous danger signals massively released from PDT-treated tumors. Toll-like receptors, localized predominantly in the membrane of immune cells, are the major sensors of the recognition arm of the innate immune system. The engagement of these receptors by PDT-generated danger signals prompts the activation of the networks of innate immunity signaling pathways leading to the downstream activation of nuclear transcription factors responsible for the transcription of inflammatory/immune response-associated genes. The contribution of PDT-induced host response to the therapeutic outcome depends on the balance between the tissue-destructive action of inflammatory/immune effectors and the impact of concomitantly mobilized negative regulatory mechanisms evolved for controlling the intensity and duration of inflammatory and immune responses.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1995-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1999-12-01

    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.

  5. Photodynamic therapy for the treatment of induced mammary tumor in rats.

    PubMed

    Ferreira, Isabelle; Ferreira, Juliana; Vollet-Filho, José Dirceu; Moriyama, Lilian T; Bagnato, Vanderlei S; Salvadori, Daisy Maria Favero; Rocha, Noeme S

    2013-02-01

    The objective of this work was to evaluate photodynamic therapy (PDT) by using a hematoporphyrin derivative as a photosensitizer and light-emitting diodes (LEDs) as light source in induced mammary tumors of Sprague-Dawley (SD) rats. Twenty SD rats with mammary tumors induced by DMBA were used. Animals were divided into four groups: control (G1), PDT only (G2), surgical removal of tumor (G3), and submitted to PDT immediately after surgical removal of tumor (G4). Tumors were measured over 6 weeks. Lesions and surgical were LEDs lighted up (200 J/cm(2) dose). The light distribution in vivo study used two additional animals without mammary tumors. In the control group, the average growth of tumor diameter was approximately 0.40 cm/week. While for PDT group, a growth of less than 0.15 cm/week was observed, suggesting significant delay in tumor growth. Therefore, only partial irradiation of the tumors occurred with a reduction in development, but without elimination. Animals in G4 had no tumor recurrence during the 12 weeks, after chemical induction, when compared with G3 animals that showed 60 % recurrence rate after 12 weeks of chemical induction. PDT used in the experimental model of mammary tumor as a single therapy was effective in reducing tumor development, so the surgery associated with PDT is a safe and efficient destruction of residual tumor, preventing recurrence of the tumor. PMID:22565345

  6. Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

    PubMed

    Nair, Lakshmi V; Nazeer, Shaiju S; Jayasree, Ramapurath S; Ajayaghosh, Ayyappanpillai

    2015-06-23

    Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 ?g (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC. PMID:25970038

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

    SciTech Connect

    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

    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.

  8. Combination of phosphatidylinositol 3-kinases pathway inhibitor and photodynamic therapy in endothelial and tumor cells.

    PubMed

    Fateye, Babasola; Li, Weihua; Wang, Chenguang; Chen, Bin

    2012-01-01

    Tumor recurrence due to incomplete eradication of tumor cells is a major problem facing current cancer therapies. To overcome this problem, it is necessary to enhance cell killing and/or prevent cell regrowth after treatment. Because phosphatidylinositol 3-kinases (PI3K) pathway plays an important role in stimulating cell survival and growth, we studied the feasibility of using a PI3K pathway inhibitor NVP-BEZ235 (BEZ235) to enhance the effectiveness of vascular-targeted photodynamic therapy (vPDT) with verteporfin. We found that BEZ235 or PDT alone significantly inhibited cell growth in both SVEC endothelial and PC-3 prostate cancer cells, although SVEC cells appeared to be more responsive than PC-3 cells. Autophagy was detected after both BEZ235 and verteporfin-PDT in both cell lines. Autophagy appeared to protect cells from PDT-induced cell death because inhibition of autophagy increased cell death. Autophagic flux assay revealed that PDT actually decreased autophagic flux especially at a high dose of verteporfin. Combination of BEZ235 and PDT caused greater inhibition of PI3K signaling pathway, leading to enhanced cell growth inhibition in both cell lines. SVEC cells exhibited a higher sensitivity towards such a combination than PC-3 cells. Our data indicated that BEZ235 in combination with PDT provides a promising approach of enhancing therapeutic response. PMID:22506666

  9. Designing multi-branched gold nanoechinus for NIR light activated dual modal photodynamic and photothermal therapy in the second biological window.

    PubMed

    Vijayaraghavan, Priya; Liu, Cheng-Hong; Vankayala, Raviraj; Chiang, Chi-Shiun; Hwang, Kuo Chu

    2014-10-22

    Gold nanoechinus can sensitize the formation of singlet oxygen in the first and the second near-infra red (NIR) biological windows and exert in vivo dual modal photodynamic and photothermal therapeutic effects (PDT and PTT) to destruct the tumors completely. This is the first literature example of the destruction of tumors in NIR window II induced by dual modal nanomaterial-mediated photodynamic and photothermal therapy (NmPDT & NmPTT). PMID:25042520

  10. The Influence of Endocrine Effects of Adjuvant Therapy on Quality of Life Outcomes in Younger Breast Cancer Survivors

    Microsoft Academic Search

    M. Tish Knobf

    2006-01-01

    Significance. There are 2.2 million breast cancer survi- vors, and approximately 25%-30% of newly diagnosed women each year are <50 years of age. Adjuvant therapy has prolonged survival, but the quality of that survival is influenced by persistent and late effects of therapy. Knowledge of treatment outcomes will assist in the design of interventions to prevent or manage persistent and

  11. Hyperbaric oxygen therapy augments the photodynamic action of methylene blue against bacteria in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, S. K.; Dadani, F. N.; Chien, C.; Wilson, B. C.

    2007-02-01

    Photodynamic therapy (PDT) entails the combination of photosensitizer and light to generate cytotoxic molecules that derive from molecular oxygen (O II). The presence of sufficient O II within the target tissues is critical to the efficiency of PDT. This study investigates the use of hyperbaric oxygen therapy in combination with PDT (HOTPDT) to augment the photodynamic action of methylene blue (MB) or 5-aminolevulinic acid (ALA) against gram positive and gram negative bacterial strains in vitro. Staphylococcus aureus or Pseudomonas aeruginosa were grown in trypticase soy broth as planktonic cultures (~10 8/mL) or as established biofilms in 48 well plates (3 days old) at 32°C. Dark toxicity and PDT response in the presence or absence of HOT (2 atmospheres, 100% O II for 30, 60 or 120 min) was established for both MB (0-0.1 mM) and ALA (0- 1 mM) for a range of incubation times. The number of surviving colonies (CFU/mL) was plotted for each treatment groups. Light treatments (5, 10, 20 or 30 J/cm2) were conducted using an array of halogen bulbs with a red filter providing 90% transmittance over 600-800 nm at 21 mW/cm2. HOT increased the dark toxicity of MB (30 min, 0.1 mM) from < 0.2 log cell kill to 0.5 log cell kill. Dark toxicity of ALA (4 hr, 1 mM) was negligible and did not increase with HOT. For non-dark toxic concentrations of MB or ALA, (0.05 mM and 1 mM respectively) HOT-PDT enhanced the antimicrobial effect of MB against Staphylococcus aureus in culture by >1 and >2 logs of cell kill (CFU/mL) at 5 and 10 J/cm2 light dose respectively as compared to PDT alone. HOT-PDT also increased the anti-microbial effects of MB against Staphylococcus aureus biofilms compared to PDT, albeit less so (> 2 logs) following 10 J/cm2 light dose. Anti-microbial effects of PDT using ALA were not significant for either strain with or without HOT. These data suggest that HOTPDT may be useful for improving the PDT treatment of bacterial infections.

  12. Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

    SciTech Connect

    Thomas, P.R.; Lindblad, A.S.; Stablein, D.M.; Knowlton, A.H.; Bruckner, H.W.; Childs, D.S.; Mittelman, A.

    1986-03-15

    An adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

  13. Gold nanorod-photosensitizer complex obtained by layer-by-layer method for photodynamic/photothermal therapy in vitro.

    PubMed

    Kim, Seung Beom; Lee, Tae Heon; Yoon, Il; Shim, Young Key; Lee, Woo Kyoung

    2015-03-01

    Gold nanorod (GNR)-photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin-18) and cationic poly(allylamine hydrochloride) by layer-by-layer method, and was characterized by transmission electron microscopy, UV-vis spectroscopy, and zeta potential. The GNR-PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT. PMID:25630881

  14. An unusual form of Naxos disease and its improvement by adjuvant low-dose colchicine therapy.

    PubMed

    Gultekin, Nazmi; Kucukates, Emine

    2013-08-01

    We evaluated a female patient with an unusual form of Naxos disease, who presented with central cyanosis and clubbing, simulating congenital heart disease. Adjuvant low-dose colchicine therapy (0.5 mg once daily) showed positive effects and has been continued for six months. Colchicine has anti-inflammatory and anti-fibrotic properties. It inhibits mitosis by disrupting tubulin assembly and enhances cellular apoptosis. Follow-up showed improvement in the patient's clinical status, with a dramatic disappearance of the electrical storm and reductions in cyanosis and palmoplantar hyperkeratosis. Low-dose colchicine may be safe and effective in patients with Naxos disease and may reduce related complications. PMID:24187773

  15. Two-photon photodynamic therapy of C6 cells by means of 5-aminolevulinic acid induced protoporphyrin IX.

    PubMed

    Beck, Tobias J; Burkanas, Marius; Bagdonas, Saulius; Krivickiene, Zita; Beyer, Wolfgang; Sroka, Ronald; Baumgartner, Reinhold; Rotomskis, Ricardas

    2007-06-26

    Photodynamic therapy (PDT) has received increased attention as a treatment modality for malignant tumors as well as non-oncologic diseases such as age-related macular degeneration (AMD). An alternative to excite the photosensitizer by the common one-photon absorption is the method of two-photon excitation (TPE). This two-photon photodynamic therapy has the potential of improving the therapeutic outcome due to a highly localized photodynamic effect. The present study investigated the two-photon excited PDT performing in vitro experiments where C6 rat glioma cells were irradiated with a pulsed and focused fs Ti:sapphire laser emitting light at 800 nm. The irradiance distribution of the laser beam was carefully analyzed before the experiment and the applied irradiance was known for each position within the irradiated cell layer. Cells were divided into four groups and one group was incubated with 5-ALA and irradiated 4-5h later. The survival of this group was tested after irradiation by means of ethidium bromide and acridine orange staining and compared to a control group, which was irradiated under the same conditions, but not incubated with 5-ALA before. Both groups showed necrotic areas depending on the applied irradiance, the value of which at the margin of the necrotic area could be deduced from its size. 5-ALA incubated cells became necrotic after irradiation with a mean irradiance above 6.1 x 10(10) W/cm(2), while non-incubated cells remained viable. Cells of both groups became necrotic when treated with an irradiance above 10.9 x 10(10) W/cm(2). The observed affected area of the cell layers was between 0.13 mm(2) and 1.10 mm(2). Since the irradiation of non-incubated cells below the mean power density of 10.9 x 10(10) W/cm(2) induced no necrosis, apparently no thermal damage was induced in the cells and necrosis of the 5-ALA incubated cells can be ascribed to the photodynamic effect induced by two-photon excitation. The successful photodynamic treatment of a large area of a monolayer cell culture induced by two-photon excitation offers new perspectives for photodynamic treatment modalities. PMID:17513121

  16. Photodynamic therapy can induce non-specific protective immunity against a bacterial infection

    NASA Astrophysics Data System (ADS)

    Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Kinoshita, Manabu; Morimoto, Yuji; Hamblin, Michael R.

    2012-03-01

    Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X107 CFU) into the mouse knee followed 3 days later by 1 ?g of Photofrin and 635- nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection.

  17. Treatment of squamous cell carcinoma of the lip using Foscan-mediated photodynamic therapy.

    PubMed

    Kübler, A C; de Carpentier, J; Hopper, C; Leonard, A G; Putnam, G

    2001-12-01

    Carcinoma of the lip is a common cancer of the head and neck area; its incidence is approximately one-quarter that for oral cavity cancers. It occurs most frequently on the lower lip of elderly males. This non-randomized Phase II study aimed to estimate the complete response (CR) rate to Foscan-mediated photodynamic therapy (Foscan-PDT) in patients with primary cancer of the lip, duration of CR, and the tolerability and safety of Foscan-PDT. Twenty-five patients with squamous cell carcinoma (SCC) of the lip (Tis, T1, T2/N0/M0) and Karnofsky status > or = 70 received 0.15 mg/kg Foscan intravenously, followed 4 days later by a single non-thermal illumination of the tumour (light dose 20 J/cm2, irradiance 100 mW/cm2, lambda=652 nm). Response was determined after 12 weeks and mean follow up is 424 days so far. After 12 weeks, 96% of cases (24/25) showed CR, and all CRs were confirmed by biopsy. The most common adverse event was swelling and local pain at the treatment site. Tumour recurrence was observed in two patients 4 and 18 months after PDT. One patient developed a single lymph node metastasis 7 months after therapy. Photosensitivity reactions occurred in five patients. The functional results were excellent in all patients without any signs of limited mouth opening or impaired lip closure. The cosmetic outcome was better than after surgical therapy. Foscan-PDT is an effective treatment modality for small primary tumours of the lips. Foscan-PDT yields complete response rates comparable to those published for surgery or radiotherapy without causing major toxicity. It allows preservation of form and function and does not compromise future treatment options for recurrent, residual or second primary disease. PMID:11829232

  18. Photodynamic therapy with porphyrin and phthalocyanine sensitisation: quantitative studies in normal rat liver.

    PubMed Central

    Bown, S. G.; Tralau, C. J.; Smith, P. D.; Akdemir, D.; Wieman, T. J.

    1986-01-01

    Selective sensitisation of malignant tumours to monochromatic light (photodynamic therapy, PDT) is a promising approach to cancer treatment, but current sensitisers are unsatisfactory and the parameters controlling effects produced in normal and neoplastic tissue are poorly understood. To quantify the effects in a relatively homogeneous organ, we carried out experiments in the livers of normal rats following systemic sensitisation with haematoporphyrin derivative (HpD) and a new sensitiser, a sulphonated aluminium phthalocyanine (AlSPc) using light from an Argon pumped tunable dye laser. Damage from PDT (dominant at 100 mW laser power) could be distinguished from that due to local hyperthermia (dominant at 400 mW). For both sensitisers, the extent of PDT necrosis increased with the applied light energy and was abolished by occluding the hepatic blood flow during therapy. With HpD, the extent of PDT necrosis was maximum with only a few hours between sensitisation and therapy, and was not detectable when this interval was increased to a week. With AlSPc, the extent of necrosis in liver changed little with sensitisation times from 1 h to 1000 h (6 weeks), and declined slowly thereafter, matching the amount of AlSPc measurable by alkali extraction, although prolonged photosensitisation was not seen with AlSPc in muscle. Less cutaneous photosensitivity was seen with AlSPc than with HpD. AlSPc is easier to produce and handle than HpD, has a more appropriate strong absorption peak (at 675 nm) and from these results, warrants further study as a photosensitiser for PDT. Images Figure 4 PMID:2942166

  19. Higher Irradiance and Photodynamic Therapy for Age-Related Macular Degeneration (An AOS Thesis)

    PubMed Central

    Miller, Joan W.

    2008-01-01

    Purpose Photodynamic therapy (PDT) using verteporfin was the first pharmacologic therapy for neovascular age-related macular degeneration and changed the treatment paradigm for a major, blinding disease. The experimental work in the nonhuman primate was essential in developing treatment parameters for verteporfin PDT that could successfully occlude choroidal neovascularization with limited injury to the neural retina. Early in the preclinical primate studies, we hypothesized that higher irradiances could be used for ocular PDT than had been used in dermatology and other applications, which typically utilized an irradiance of 150 to 200 mW/cm2. We set out to test the feasibility of irradiances up to 1800 mW/cm2. Methods PDT was applied to normal monkey eyes using verteporfin/benzoporphyrin derivative (BPD) (2 mg/kg) mixed with low-density lipoprotein in DMSO, and 692-nm light, with a spot size 1250?m, fluence approximately 50 J/cm2, and irradiance varying from 150 (treatment time, 6 minutes) to 1800 mW/cm2 (treatment time, 30 seconds). Photocoagulation lesions were applied using 514-nm and 692-nm laser light without drug, with irradiance of 18,750 to 200,000 mW/cm2 and spot size of 500 ?m. Treatment effect was evaluated by fundus photography, angiography, and light and electron microscopy with collagen denaturation as a marker of thermal injury. Results Verteporfin/BPD PDT at irradiances of 150 to 1800 mW/cm2 showed no collagen denaturation in contrast to photocoagulation lesions without dye (irradiance 10-fold and higher). Conclusions Verteporfin PDT could safely be performed at higher irradiances, permitting a clinically practical therapy. Ultimately, clinical trials demonstrated that verteporfin PDT could limit moderate vision loss in neovascular age-related macular degeneration. Although anti-VEGF therapy has replaced PDT as a first-line therapy, PDT may still have a role, perhaps in combination therapies. Further investigations to optimize drug delivery and to better understand the molecular mechanisms of PDT effects in both choroidal neovascularization and retina will improve its application in macular diseases. PMID:19277246

  20. Radiation therapy and photodynamic therapy for biliary tract and ampullary carcinomas

    Microsoft Academic Search

    Hiroya Saito; Tadahiro Takada; Masaru Miyazaki; Shuichi Miyakawa; Kazuhiro Tsukada; Masato Nagino; Satoshi Kondo; Junji Furuse; Toshio Tsuyuguchi; Fumio Kimura; Hideyuki Yoshitomi; Satoshi Nozawa; Masahiro Yoshida; Keita Wada; Hodaka Amano; Fumihiko Miura

    2008-01-01

    The purpose of radiation therapy for unresectable biliary tract cancer is to prolong survival or prolong stent patency, and\\u000a to provide palliation of pain. For unresectable bile duct cancer, there are a number of studies showing that radiation therapy\\u000a is superior to the best supportive care. Although radiation therapy is used in many institutions, no large randomized controlled\\u000a trials (RCTs)

  1. Targeted in vivo photodynamic therapy with epidermal growth factor receptor-specific peptide linked nanoparticles.

    PubMed

    Narsireddy, Amreddy; Vijayashree, Kurra; Irudayaraj, Joseph; Manorama, Sunkara V; Rao, Nalam M

    2014-08-25

    In targeted photodynamic therapy (tPDT), photosensitizers (PS) are targeted to disease tissue to reduce the dosage of PS and in addition to reduce the photo damage to the non-target tissue. We synthesized iron oxide nanoparticles (NP) armored with tumor targeting peptide and PS for targeted PDT. Chitosan covered Fe3O4 NPs (30 nm) were deposited with gold NPs to generate two distinct chemical surfaces. To the gold particles PS was attached with a lipoic acid linker. Human epidermal growth factor receptor (hEGFR)-specific peptide was also attached to the same particles via a nickel-nitrilotriacetic acid linker attached to the chitosan. Using these nanoparticles, peptide specific uptake and PDT mediated cell death of the SK-OV-3 cells (Her2(+) positive cells) were demonstrated by confocal microscopy, T2 imaging and viability assays. Peptide mediated preferential distribution of these NPs into tumor tissue was also shown in a xenograft tumor model. After one intravenous injection and one PDT dose, peptide bound NPs retarded tumor growth significantly compared to dark controls or treatments with NPs without peptide. The tumor retardation by targeted NPs was achieved at a PS concentration of 3.9 nmol/animal, whereas similar effect was seen with free PS at 220 nmol/animal. Therapeutic potential of these peptide containing NPs would be a useful in targeted PDT and in imaging the target tissue. PMID:24939618

  2. Illumination devices for uniform delivery of light to the oral cavity for photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    To date, the lack of light delivery mechanisms to the oral cavity remains a barrier to the treatment of oral cancer with photodynamic therapy (PDT). The greatest impediment to medical practitioners is the current need to shield the normal tissues of the oral cavity, a costly and time-consuming procedure. In this research, we present the design of illumination devices to deliver light to the oral cavity for PDT, which will facilitate administration of PDT in the clinic. The goal for such an illumination device, as indicated by our clinical collaborators at Roswell Park Cancer Institute in Buffalo, NY, is to limit exposure of healthy tissue and produce an average irradiance of 100 mW/cm2 over the treatment field, with spatial non-uniformities below 10%. Furthermore, the size of the device must be compact to allow use in the oral cavity. Our research led to the design and fabrication of two devices producing spatial non-uniformities below 6% over a treatment area of 0.25 cm2 by design. One device consisted of an appropriately-sized reflector, inspired by solar concentrators, illuminated by a cylindrical diffusing fiber optimally located within the reflector; another was a solid lightpipe with a combination of optimized tapered and straight components.

  3. Gold Nanocage-Photosensitizer Conjugates for Dual-Modal Image-Guided Enhanced Photodynamic Therapy

    PubMed Central

    Srivatsan, Avinash; Jenkins, Samir V.; Jeon, Mansik; Wu, Zhijin; Kim, Chulhong; Chen, Jingyi; Pandey, Ravindra K.

    2014-01-01

    We have demonstrated that gold nanocage-photosensitizer conjugates can enable dual image-guided delivery of photosensitizer and significantly improve the efficacy of photodynamic therapy in a murine model. The photosensitizer, 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide (HPPH), was noncovalently entrapped in the poly(ethylene glycol) monolayer coated on the surface of gold nanocages. The conjugate is stable in saline solutions, while incubation in protein rich solutions leads to gradual unloading of the HPPH, which can be monitored optically by fluorescence and photoacoustic imaging. The slow nature of the release in turn results in an increase in accumulation of the drug within implanted tumors due to the passive delivery of gold nanocages. Furthermore, the conjugate is found to generate more therapeutic singlet oxygen and have a lower IC50 value than the free drug alone. Thus the conjugate shows significant suppression of tumor growth as compared to the free drug in vivo. Short-term study showed neither toxicity nor phenotypical changes in mice at therapeutic dose of the conjugates or even at 100-fold higher than therapeutic dose of gold nanocages. PMID:24465274

  4. A study of the effects of photodynamic therapy on the normal tissues of the rabbit jaw.

    PubMed Central

    Meyer, M.; Speight, P.; Bown, S. G.

    1991-01-01

    Photodynamic therapy (PDT) is an anti-cancer treatment which involves the systemic administration of a photosensitising drug which is preferentially absorbed by tumour tissue. Relatively little drug should be absorbed by the surrounding normal tissues. Tumour destruction is achieved when the tumour is illuminated with light of a wavelength which activates the photosensitising drug thereby inducing a cytotoxic reaction. However studies in many tissues have shown that the hoped for tumour selectivity is rarely achieved. Using the rabbit mandible and gingiva as our models we have studied the effects of various doses of PDT on the tissues of the oral cavity, namely mucosa, bone, muscle and salivary gland. The photosensitiser used was di-sulphonated aluminium phthalocyanine. Results show that whereas bone is extremely resistant to PDT the other tissues are vulnerable to it. In the case of muscle and salivary gland this susceptibility is very much dose related. In salivary tissue necrotising sialometaplasia was observed in areas of the gland adjacent to those that had undergone necrosis. All tissues were noted to heal or regenerate well following PDT injury. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:1764372

  5. Iron Chelators in Photodynamic Therapy Revisited: Synergistic Effect by Novel Highly Active Thiosemicarbazones

    PubMed Central

    2014-01-01

    In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe2+ forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe2+ affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX. PMID:24900837

  6. Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light.

    PubMed

    Yu, Guoqiang; Durduran, Turgut; Zhou, Chao; Zhu, Timothy C; Finlay, Jarod C; Busch, Theresa M; Malkowicz, S Bruce; Hahn, Stephen M; Yodh, Arjun G

    2006-01-01

    Photodynamic therapy (PDT) requires oxygen to cause cellular and vascular tumor damage. Tissue oxygen concentration, in turn, is influenced by blood flow and blood oxygenation. Real-time clinical measurement of these hemodynamic quantities, however, is rare. This paper reports the development and application of a probe, combining diffuse reflectance spectroscopy (DRS) for measurement of tumor blood oxygenation and diffuse correlation spectroscopy (DCS) for measurement of tumor blood flow. The instrument was adapted for clinical use during interstitial prostate PDT. Three patients with locally recurrent prostate cancer received 2 mg/ kg motexafin lutetium (MLu) 3 h before illumination and a total light dose of 100 J/cm(2) at 150 mW/cm. Prostrate blood oxygen saturation (StO2) decreased only slightly (approximately 3%) after treatment. On the other hand, prostate blood flow and total hemoglobin concentration over the course of PDT decreased by 50% and 15%, respectively, suggesting MLu-mediated PDT has an anti-vascular effect. While it is certainly impossible to draw definite conclusions from measurements of only three patients, the observed differences in tumor blood flow and blood oxygenation responses during PDT can, in principle, be used to choose among tissue oxygen consumption models and therefore emphasize the potential clinical value for simultaneous monitoring of both parameters. PMID:16696593

  7. Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Ohashi, Shinya; Kikuchi, Osamu; Tsurumaki, Mihoko; Nakai, Yukie; Kasai, Hiroi; Horimatsu, Takahiro; Miyamoto, Shin'ichi; Shimizu, Akira; Chiba, Tsutomu; Muto, Manabu

    2014-01-01

    Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC. PMID:25090101

  8. Immunogenic Cell Death: Can It Be Exploited in PhotoDynamic Therapy for Cancer?

    PubMed Central

    Panzarini, Elisa; Inguscio, Valentina; Dini, Luciana

    2013-01-01

    Immunogenic Cell Death (ICD) could represent the keystone in cancer management since tumor cell death induction is crucial as well as the control of cancer cells revival after neoplastic treatment. In this context, the immune system plays a fundamental role. The concept of Damage-Associated Molecular Patterns (DAMPs) has been proposed to explain the immunogenic potential of stressed or dying/dead cells. ICD relies on DAMPs released by or exposed on dying cells. Once released, DAMPs are sensed by immune cells, in particular Dendritic Cells (DCs), acting as activators of Antigen-Presenting Cells (APCs), that in turn stimulate both innate and adaptive immunity. On the other hand, by exposing DAMPs, dying cancer cells change their surface composition, recently indicated as vital for the stimulation of the host immune system and the control of residual ill cells. It is well established that PhotoDynamic Therapy (PDT) for cancer treatment ignites the immune system to elicit a specific antitumor immunity, probably linked to its ability in inducing exposure/release of certain DAMPs, as recently suggested. In the present paper, we discuss the DAMPs associated with PDT and their role in the crossroad between cancer cell death and immunogenicity in PDT. PMID:23509727

  9. Measurements of the optical properties of tissue in conjunction with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Nilsson, Annika M. K.; Berg, Roger; Andersson-Engels, Stefan

    1995-07-01

    A simple optical dosimeter was used to measure the light intensity in rat liver and muscle in vivo with fibers positioned at different depths to investigate whether the light penetration changed during photodynamic therapy (PDT). The results were then correlated with measurements of the three optical-interaction coefficients mu s, mu a, and g for wavelengths in the range 500-800 nm for PDT-treated and nontreated rat liver and muscle tissue in vitro. A distinct increase in the absorption coefficient was seen immediately after treatment, in agreement with the decreasing light intensity observed during the treatment, as measured with the optical dosimeter. The collimated transmittance was measured with a narrow-beam setup, and an optical integrating sphere was used to measure the diffuse reflectance and total transmittance of the samples. The corresponding optical properties were obtained by spline interpolation of Monte Carlo-simulated data. To ensure that the measured values were correct, we performed calibration measurements with suspensions of polystyrene microspheres and ink.

  10. Enhanced Systemic Immune Reactivity to a Basal Cell Carcinoma Associated Antigen Following Photodynamic Therapy

    PubMed Central

    Kabingu, Edith; Oseroff, Allan R.; Wilding, Gregory E.; Gollnick, Sandra O.

    2009-01-01

    Purpose Numerous pre-clinical studies have demonstrated that local photodynamic therapy (PDT) of tumors enhances systemic anti-tumor immunity. However other than single case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma (BCC) resulted in an increased systemic immune response to a BCC associated tumor antigen, Hip1. Experimental Design BCC lesions were treated with either PDT or surgically removed. Blood was collected from patients immediately before or 7–10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2 expressing patients and reactivity to an HLA-A2 restricted Hip1 peptide was measured by interferon-? ELISpot assay. Results Immune recognition of Hip1 increased in patients whose BCC lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared to patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. Conclusions These findings represent the first demonstration that local tumor PDT can enhance systemic immune responses to tumors in patients and validate previous preclinical findings. PMID:19549769

  11. In vitro photodynamic therapy of MG-63 osteosarcoma cells mediated by aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent M.; White, Bradley M.; Newton, Mariko J.; Jacques, Steven L.; Baugher, Paige J.

    2011-02-01

    This is an in vitro study of photodynamic therapy (PDT) in the MG-63 line of human osteosarcoma cells, as mediated by aminolevulinic acid (ALA). The primary goal of this work is to determine the feasibility and effectiveness of treating osteosarcoma through PDT. In addition, this work is aimed at determining whether the resulting cell death occurs through apoptosis or cellular necrosis. The MG-63 cells are treated with increasing concentrations of ALA from 0.1-10 mM ALA, leading to the accumulation of the photosensitizer protoporphyrin IX (PpIX) within the cells. After incubation periods of 4 and 24 hours in ALA, the cells are illuminated by 0-10 J/cm2 of 636 nm light in order to activate the PpIX and induce oxidative damage to the cells. Light is administered by an 8x12 array of LED's, which are controlled by an Arduino Duemilanove microcontroller board in order to assure ease of use along with accurate levels of exposure. Controls for this experiment include 0 J/cm2 of light exposure for all experimental concentrations of ALA, as well as illuminating cells that have not been incubated in ALA at all experimental levels of illumination. MG-63 cells are analyzed through fluorimetry and MTT assays in order to determine the effectiveness of ALA mediated PDT of osteosarcoma.

  12. The ratio of the spherical and flat Detectors at tissue surfaces during pleural photodynamic therapy

    PubMed Central

    Zhu, Timothy C; Friedberg, Joseph S; Dimofte, Andrea; Miles, Jeremy; Metz, James; Glatstein, Eli; Hahn, Stephen M

    2015-01-01

    An isotropic detector-based system was compared with a flat photodiode-based system in patients undergoing pleural photodynamic therapy. Isotropic and flat detectors were placed side by side in the chest cavity, for simultaneous in vivo dosimetry at surface locations for twelve patients. The treatment used 630nm laser to a total light irradiance of 30 J/cm2 (measured with the flat photodiodes) with photofrin® IV as the photosensitizer. Since the flat detectors were calibrated at 532nm, wavelength correction factors (WCF) were used to convert the calibration to 630nm (WCF between 0.542 and 0.703). The mean ratio between isotropic and flat detectors for all sites was linear to the accumulated fluence and was 3.4±0.6 or 2.1±0.4, with or without the wavelength correction for the flat detectors, respectively. The ?eff of the tissues was estimated to vary between 0.5 to 4.3 cm?1 for four sites (Apex, Posterior Sulcus, Anterior Chest Wall, and Posterior Mediastinum) assuming ?s? = 7 cm?1. Insufficient information was available to estimate ?eff directly for three other sites (Anterior Sulcus, Posterior Chest Wall, and Pericardium) primarily due to limited sample size, although one may assume the optical penetration in all sites to vary in the same range (0.5 to 4.3 cm?1).

  13. Insights into Photodynamic Therapy Dosimetry: Simultaneous Singlet Oxygen Luminescence and Photosensitizer Photobleaching Measurements

    PubMed Central

    Jarvi, Mark T.; Patterson, Michael S.; Wilson, Brian C.

    2012-01-01

    Photodynamic therapy (PDT) is generally based on the generation of highly reactive singlet oxygen (1O2) through interactions of photosensitizer, light, and oxygen (3O2). These three components are highly interdependent and dynamic, resulting in variable temporal and spatial 1O2 dose deposition. Robust dosimetry that accounts for this complexity could improve treatment outcomes. Although the 1270 nm luminescence emission from 1O2 provides a direct and predictive PDT dose metric, it may not be clinically practical. We used 1O2 luminescence (or singlet oxygen luminescence (SOL)) as a gold-standard metric to evaluate potentially more clinically feasible dosimetry based on photosensitizer bleaching. We performed in vitro dose-response studies with simultaneous SOL and photosensitizer fluorescence measurements under various conditions, including variable 3O2, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). The results show that SOL was always predictive of cytotoxicity and immune to PDT's complex dynamics, whereas photobleaching-based dosimetry failed under hypoxic conditions. However, we identified a previously unreported 613 nm emission from mTHPC that indicates critically low 3O2 levels and can be used to salvage photobleaching-based dosimetry. These studies improve our understanding of PDT processes, demonstrate that SOL is a valuable gold-standard dose metric, and show that when used judiciously, photobleaching can serve as a surrogate for 1O2 dose. PMID:22325290

  14. In vitro study on methemoglobin formation in erythrocytes following hexyl-aminolevulinate induced photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2007-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as hexyl-aminolevulinate (HAL) may increase the efficiency of PDT. HAL penetrates into the cell where the photosensitizer protoporphyrin IX (PPIX) is produced endogenously. In a previous study on HAL based PDT treatment of rat bladder cancer (AY-27 transitional cell carcinoma), a depression of the optical reflectance spectra after treatment was observed in some of the animals. This depression of the spectra was caused by metHemoglobin (metHb). MetHb is an indication of oxidative stress, and can be formed as a result of for instance UV-radiation and heating of blood. The aim of this study was to identify if metHb can be formed in vitro as a result of oxidative stress caused by singlet oxygen and ROS produced during PDT. Methemoglobin formed during PDT might thus be used as an indirect measure of the photochemical processes. This may help predict the PDT treatment outcome. Red blood cells mixed with AY-27 cells exposed to HAL, or PPIX received light treatment, and the changes in the absorption spectra were measured spectrophotometrically. The methemoglobin absorbance spectrum was also studied, and found to be strongly dependant on pH. Hemolysis of erythrocytes by PDT was found, however no metHb was formed in vitro.

  15. A medical manipulator system with lasers in photodynamic therapy of port wine stains.

    PubMed

    Wang, Xingtao; Tian, Chunlai; Duan, Xingguang; Gu, Ying; Huang, Naiyan

    2014-01-01

    Port wine stains (PWS) are a congenital malformation and dilation of the superficial dermal capillary. Photodynamic therapy (PDT) with lasers is an effective treatment of PWS with good results. However, because the laser density is uneven and nonuniform, the treatment is carried out manually by a doctor thus providing little accuracy. Additionally, since the treatment of a single lesion can take between 30 and 60 minutes, the doctor can become fatigued after only a few applications. To assist the medical staff with this treatment method, a medical manipulator system (MMS) was built to operate the lasers. The manipulator holds the laser fiber and, using a combination of active and passive joints, the fiber can be operated automatically. In addition to the control input from the doctor over a human-computer interface, information from a binocular vision system is used to guide and supervise the operation. Clinical results are compared in nonparametric values between treatments with and without the use of the MMS. The MMS, which can significantly reduce the workload of doctors and improve the uniformity of laser irradiation, was safely and helpfully applied in PDT treatment of PWS with good therapeutic results. PMID:25302297

  16. Photodynamic therapy (PDT) of endometrium primary cultures serving as an in-vitro model for endometriosis

    NASA Astrophysics Data System (ADS)

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

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  17. Interesting method for the synthesis of monofunctionalized phthalocyanines via subphthalocyanines for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Senz, Rainier G.; Herter, Ralf

    1995-01-01

    The photodynamic therapy (PDT) of cancer is based on the reaction of dyes, light and oxygen in tumorous tissue. Currently, mainly two different photosensitizers [Photofrin II and Hematoporphyrine derivatives (HPD)] are used in clinical investigations. They are far from being ideal for this purpose as they do not have the required specificity and the absorption maxima do not lie in the ideal region of 760 nm (maximum transmission for human tissue). These properties could potentially be improved by monofunctionalization of the photosensitizers which would allow them to be coupled with tumor specific antibodies. Also, variation of the peripheric substituents would lead to a shift in the absorption maxima to a point nearer to 760 nm. By modification of the methods found in the literature it has been possible to synthesize two new subphthalocyanines and one new subnaphthalocyanine. Starting by reacting 3,6-Dihydroxyphthalicaciddinitrile, 3,6-Dibutyloxyphthalodi-nitrile or 2,3- Dicyanonaphthalene with boron trichloride in a solvent with a high boiling point, it has been possible to form the subphthalocyanines (I) and subnaphthalocyanine (II).

  18. Transcutaneous photodynamic therapy delays the onset of paralysis in a murine multiple sclerosis model

    NASA Astrophysics Data System (ADS)

    Hunt, David W. C.; Leong, Simon; Levy, Julia G.; Chan, Agnes H.

    1995-03-01

    Photodynamic therapy (PDT) using benzoporphyrin derivative (BPD, Verteporfin) and whole body irradiation, can affect the course of adoptively transferred experimental allergic (autoimmune) encephalomyelitis (EAE) in PL mice. Murine EAE is a T cell-mediated autoimmune disease which serves as a model for human multiple sclerosis. Using a novel disease induction protocol, we found that mice characteristically developed EAE within 3 weeks of receipt of myelin basic protein (MBP)-sensitized, in vitro-cultured spleen or lymph node cells. However, if animals were treated with PDT (1 mg BPD/kg bodyweight and exposed to whole body 15 Joules cm2 of LED light) 24 hours after receiving these cells, disease onset time was significantly delayed. PDT-treated mice developed disease symptoms 45 +/- 3 days following cell administration whereas untreated controls were affected within 23 +/- 2 days. In contrast, application of PDT 48 or 120 hours following injection of the pathogenic cells had no significant effect upon the development of EAE. Experiments are in progress to account for the protective effect of PDT in this animal model. These studies should provide evidence on the feasibility of PDT as a treatment for human autoimmune disease.

  19. Metal Oxide Nanomaterials in Nanomedicine: Applications in Photodynamic Therapy and Potential Toxicity.

    PubMed

    He, Xiaojia; Aker, Winfred G; Huang, Ming-Ju; Watts, John D; Hwang, Huey-Min

    2015-01-01

    Metal oxide nanomaterials have exhibited excellent performance as nanomedicines in photodynamic therapy (PDT) for cancer and infection treatment. Their unique and tunable physicochemical properties advance them as promising alternatives in drug delivery, early diagnosis, imaging, and treatment against various tumors and infectious diseases. Moreover, the implementation of nanophototherapy in deep tissue sites is enhanced by advancements in photosensitization technology. Notwithstanding the progress made in emerging metal oxide nanomaterials-derived PDT, the potential toxicity towards adjunct tissues associated with this approach remains challenging. Regulation and legislation have also been recommended and subsequently enacted in response to public concerns related to large-scale production, transportation, use, and disposal of those nanomaterials. Consequently, a quantitative structure-activity relationship (QSAR) paradigm has been adopted and is widely used in evaluating and predicting the side effects of nanomedicines, thus influencing their design and fabrication. This article briefly reviews the application of metal oxide nanomaterials in PDT and their associated adverse impacts as reported in recent publications. The future trends and implications of this platform in nanomedicine are also highlighted. However, more studies and efforts have to be carried out for developing novel nano-therapeutics with high selectivity, sensitivity, biocompatibility, and minimal side effects in PDT. PMID:25961519

  20. Interstitial Fluorescence Spectroscopy in the Human Prostate During Motexafin Lutetium–Mediated Photodynamic Therapy

    PubMed Central

    Zhu, Timothy C.; Dimofte, Andreea; Stripp, Diana; Malkowicz, S. Bruce; Busch, Theresa M.; Hahn, Stephen M.

    2015-01-01

    The in vivo fluorescence emission from human prostates was measured before and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). A single side-firing optical fiber was used for both the delivery of 465 nm light-emitting diode excitation light and the collection of emitted fluorescence. It was placed interstitially within the prostate via a closed transparent plastic catheter. Fitting of the collected fluorescence emission spectra using the known fluorescence spectrum of 1 mg/kg MLu in an intralipid phantom yields a quantitative measure of the local MLu concentration. We found that an additional correction factor is needed to account for the reduction of the MLu fluorescence intensity measured in vivo due to strong optical absorption in the prostate. We have adopted an empirical correction formula given by C=(3.1cm?1/µs?) exp (µeff · 0.97 cm), which ranges from approximately 3 to 16, with a mean of 9.3 ± 4.8. Using a computer-controlled step motor to move the probe incrementally along parallel tracks within the prostate we can determine one-dimensional profiles of the MLu concentration. The absolute MLu concentration and the shape of its distribution are confirmed by ex vivo assay and by diffuse absorption measurements, respectively. We find significant heterogeneity in photosensitizer concentration within and among five patients. These variations occur over large enough spatial scales compared with the sampling volume of the fluorescence emission that mapping the distribution in three dimensions is possible. PMID:16808592