Aleksandra Kawczyk-Krupka

Photodynamic therapy of premalignant lesions and local recurrence of laryngeal and hypopharyngeal cancers

Abstract The main advantage of photodynamic therapy (PDT) in laryngology seems to be its non-invasiveness and the possibility of using it despite previous application of conventional methods. In the study, we gave PDT to two separate groups of patients, i.e. five patients with advanced tumour (four of them with local recurrence (squamous cell carcinoma) after surgery and radiotherapy and one with a primary hypopharyngeal tumour) and five patients with leucoplakia. In the first group δ-aminolaevulinic acid (ALA) was administered orally (dose 3 g), while in the second, an ointment containing 10% ALA was applied locally. In both groups prior to irradiation, the tissue level of protoporphyrin IX was verified using an adapted Xillix Life instrument. All treated lesions were irradiated with an argon-pumped dye laser (dose range 100–250 J/cm2, wavelength 635 nm). In the first group, partial response was obtained. In these advanced cases, diminution of cancerous ulcerations was observed. In the leucoplakia group, complete response was achieved in four out of five treated patients. On the basis of our preliminary results, PDT may be useful in eradicating premalignant lesions of the oral cavity and in the palliation of advanced lesions of the oropharynx and larynx.

Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia

Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic.

Photodynamic therapy in treatment of cutaneous and choroidal melanoma

Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma predominantly occurs in skin, but could also be found in the mouth, iris and retina of the eye. Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. It is highly resistant to traditional chemotherapy and radiotherapy, although modern biological therapies are showing some promise. Photodynamic therapy (PDT), as a novel effective modality of the treatment of skin cancers, opens up new possibilities in melanoma treatment also. Many experimental photodynamic therapy studies were performed. The results of many experiments indicate that that photodynamic therapy may be a promising tool for adjuvant treatment in advanced melanoma.

Photodynamic therapy in colorectal cancer treatment: the state of the art in clinical trials.

BACKGROUND Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer. This review aims to give a general overview of the PDT application to colorectal cancer in the field of clinical trials to emphasize its curative, and insufficiently exploited potential. MATERIALS AND METHODS Literature on PDT for colorectal cancer with the following medical subject headings search terms: colorectal cancer, photodynamic therapy, clinical trials was reviewed. The articles were selected by their relevance to the topic. RESULTS There are many positive and promising trial results from I to II/III phase for the use of PDT in colorectal cancer both in less advanced tumors as well as in the palliative therapy of advanced lesions. CONCLUDING REMARKS PDT seems to be a safe and a feasible treatment option for colorectal cancer. Theoretical assumptions confirmed by many results of preclinical studies taking into consideration an increasing number of analyzed clinical trials, should lead to the development of optimized standards by using PDT in colorectal cancer treatment.

Chlorin-based photodynamic therapy enhances the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in bladder cancer cells

Summary Background Photodynamic therapy (PDT) is an attractive, emerging therapeutic procedure suitable for the treatment of non-muscle-invasive bladder cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that belongs to the TNF superfamily of cytokines. The ability of TRAIL to selectively induce apoptosis in cancer cells but not in normal cells promotes the development of TRAIL-based cancer therapy. However, many tumor cells are resistant to TRAIL-induced apoptosis. The purpose of the study was to overcome TRAIL-resistance in bladder cancer cells by photodynamic therapy (PDT). Material/Methods Three human bladder transitional cancer cell lines – T24, 647V and SW780 – were treated with TRAIL and/or chlorin-based PDT. The cytotoxicity was measured by MTT and LDH assays and apoptosis was detected using annexin V by flow cytometry. Results Our test confirmed that T24 and 647V bladder cancer cells are resistant to TRAIL, whereas SW780 cells are sensitive to TRAIL. Then we examined the cytotoxic and apoptotic effects of TRAIL in combination with chlorin e6-polyvinylpyrrolidone (Ce6-PVP)-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with a low dose of PDT significantly sensitizes bladder cancer cells to TRAIL-induced apoptosis. Chlorin-based PDT augments the effect of TRAIL on bladder cancer cells. Conclusions PDT with Ce6-PVP photosensitizer enhances the cytotoxic and apoptotic effects of TRAIL on bladder cancer cells. The obtained results suggest that combined treatment by TRAIL and PDT may provide the basis for a new therapeutic approach to induce cell death in bladder cancer.

Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in dermatology: “How we do it”

In dermatology PDT has been proven to be effective in the treatment of actinic keratoses, basal cell carcinomas (BCC), Bowens disease, superficial squamous cell carcinomas (SCC).

Photodynamic therapy (PDT) using topically applied δ-aminolevulinic acid (ALA) for the treatment of malignant skin tumors

BACKGROUND The objective of our study was to determine therapeutic response to photodynamic therapy (PDT) and adverse reaction of PDT in 126 patients with 141 lesions: 36 patients with 41 lesions of superficial basal cell carcinoma (BCC), 35 patients with nodular BCC, 42 patients with ulcerated BCC, four patients with 14 lesions of actinic keratoses, five with superficial squamous cell carcinoma (SCC) and four with Bowens disease. METHODS Patients with skin malignancies were treated using 20% aminolevulinic acid (ALA) (Medac GmbH, Wedel, Germany) topically and light from an argon-pumped dye laser. RESULTS A complete response was achieved in 81.5% treated lesions. A partial response after PDT in 10.6% treated lesions, no response in 7.8% treated lesions and 11.3% lesions recurrences during 10-36 months follow-up were observed. Following light exposure skin lesions became necrotic and showed hemorrhagic crusts and the cosmetic outcome was excellent or good in 97 of the completely responding lesions (84.3%). CONCLUSIONS Clinical studies reported by other groups have shown similar high percentages of clinical cure. PDT appears to be a more feasible alternative to conventional therapy of skin malignancies.

Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

BACKGROUND Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer (CRC). This review aims to give a general overview of preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment to emphasize their potential in study of PDT mechanism, safety and efficiency to translate these results into clinical benefit in CRC treatment. MATERIALS AND METHOD Literature on in vitro preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment with the fallowing medical subject headings search terms: colorectal cancer, photodynamic therapy, photosensitizer(s), in vitro, cell culture(s), in vivo, animal experiment(s). The articles were selected by their relevance to the topic. RESULTS The majority of preclinical studies concerning possibility of PDT application in colon and rectal cancer is focused on phototoxic action of photosensitizers toward cultured colorectal tumor cells in vitro. The purposes of animal experiments are usually elucidation of mechanisms of observed photodynamic effects in scale of organism, estimation of PDT safety and efficiency and translation of these results into clinical benefit. CONCLUDING REMARKS In vitro photodynamic studies and animal experiments can be useful for studies of mechanisms and efficiency of photodynamic method as a start point on PDT clinical research. The primary disadvantage of in vitro experiments is a risk of over-interpretation of their results during extrapolation to the entire CRC.

Treatment of localized prostate cancer using WST-09 and WST-11 mediated vascular targeted photodynamic therapy-A review.

BACKGROUND Photodynamic therapy (PDT) is well known for its direct cytotoxicity of the free radical-producing photochemical reaction, indirect mechanisms of action including modulation of intrinsic anti-tumour immune activity, and occlusion of pathologically altered tumour vessels leading to tumour ischaemia. The aim of this work is to critically review the evidence base for the use of vascular targeted PDT (VTP) to treat low-risk prostate cancer, and to discuss perspectives and challenges yet to be overcome. A brief general overview of focal prostate cancer therapy was provided, followed by a discussion of both basic and clinical research pertaining to prostate cancer VTP, with a focus on the palladium-based WST-09 and WST-11 photosensitisers. MATERIALS AND METHOD Literature on VTP for prostate cancer with the fallowing medical subject headings search terms: prostate cancer, photodynamic therapy, vascular targeted photodynamic therapy, bacteriopheophorbide were reviewed. The articles were selected by their relevance to the topic. RESULTS The clinical and basic research data available to date show much promise for WST-09, and WST-11 based VTP eventually joining the standard urologists armamentarium against prostate cancer. With good reported tolerability and efficacy VTP can be proposed as an intermediate treatment for local low risk disease, halfway between watchful waiting and radical therapy.

ALA-induced photodynamic effect on vitality, apoptosis, and secretion of vascular endothelial growth factor (VEGF) by colon cancer cells in normoxic environment in vitro

BACKGROUND Cancer therapy is often based on combination of conventional methods of cancer treatment with immunotherapy. Photodynamic therapy (PDT) is one of the immunomodulating methods used in oncology. We examined how PDT influences the secretory activity of colon cancer cells in vitro, especially the secretion of vascular endothelial growth factor (VEGF) in aerobic conditions. METHODS We used two cancer cell lines with different malignancy potentials: a metastatic SW620 line and a non-metastatic SW480 line. In the first stage of the experiment, we exposed each cell line to three different concentrations of photosensitizers precursor: 5-aminolevulinic acid (ALA) and varying levels of light radiation, after which we assessed cell viability and apoptosis induction in these lines, using the MTT and LDH assays. Then, we determined the secretion of VEGF by these cells in aerobic conditions and under the ALA-PDT parameters at which cells presented the highest viability. RESULTS Photodynamic treatment with ALA did not influence on VEGF secretion by the non-metastatic SW480 cells, but caused a decrease in VEGF secretion by the metastatic SW 620 cell line by 29% (p<0.05). SW 620 cell line secreted more actively VEGF than the SW480 cells, both before and after photo dynamic therapy (p<0.05). CONCLUSION The outcome of this in vitro study presented a beneficial effect of ALA-PDT, resulting in a decrease of VEGF secretion in the more malignant SW620 cell lines. Further studies should be considered to confirm the clinical relevance of this finding.