Aleksander Sieroń

Effective photoimmunotherapy of murine colon carcinoma induced by the combination of photodynamic therapy and dendritic cells.

Purpose: The unique mechanism of tumor destruction by photodynamic therapy (PDT), resulting from apoptotic and necrotic killing of tumor cells accompanied by local inflammatory reaction and induction of heat shock proteins (HSPs), prompted us to investigate the antitumor effectiveness of the combination of PDT with administration of immature dendritic cells (DCs). Experimental Design: Confocal microscopy and Western blotting were used to investigate the influence of PDT on the induction of apoptosis and expression of HSP expression in C-26 cells. Confocal microscopy and flow cytometry studies were used to examine phagocytosis of PDT-treated C-26 cells by DCs. Secretion of interleukin (IL)-12 was measured with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard 51Cr-release assay. The antitumor effectiveness of PDT in combination with administration of DCs was investigated in in vivo model. Results: PDT treatment resulted in the induction of apoptotic and necrotic cell death and expression of HSP27, HSP60, HSP72/73, HSP90, HO-1, and GRP78 in C-26 cells. Immature DCs cocultured with PDT-treated C-26 cells efficiently engulfed killed tumor cells, acquired functional features of maturation, and produced substantial amounts of IL-12. Inoculation of immature DCs into the PDT-treated tumors resulted in effective homing to regional and peripheral lymph nodes and stimulation of cytotoxic activity of T and natural killer cells. The combination treatment with PDT and administration of DCs produced effective antitumor response. Conclusions: The feasibility and antitumor effectiveness demonstrated in these studies suggest that treatment protocols involving the administration of immature DCs in combination with PDT may have clinical potential.

Autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus

BACKGROUND The occurrence of precancerous lesions, such as high-grade dysplasia, in patients with short-segment Barretts esophagus is controversial. This study assessed the efficacy of autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barretts esophagus. METHODS A total of 34 patients (28 men, 6 women; age range 40-77 years) with histopathologically proven short-segment Barretts esophagus were studied. Autofluorescence endoscopy was performed by using monochromatized blue light (425-455 nm) filtered from a conventional xenon light source. A total of 136 and 109 biopsy specimens were taken from Barretts mucosa under control, respectively, white light endoscopy and autofluorescence endoscopy. RESULTS High-grade dysplasia was found in 9 (8.3%) autofluorescence-guided biopsy specimens, which was significantly greater than the number of white light endoscopy-guided biopsy specimens with this finding (one positive biopsy specimen, 0.7% of total biopsy specimens obtained). Autofluorescence endoscopy detected high-grade dysplasia in 7 patients, 6 more than were identified with white light endoscopy. In the one patient with high-grade dysplasia detected by white light endoscopy-guided biopsy specimens, autofluorescence-guided biopsy specimens revealed only low-grade dysplasia. CONCLUSION Autofluorescence endoscopy in patients with short-segment Barretts esophagus increases the detection rate of high-grade dysplasia.

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.

Thermography study of skin response due to whole‐body cryotherapy

Purpose: Thermography and contact thermometry were used to study the influence of body mass index (BMI) on the lowering of skin temperature caused by whole‐body cryotherapy.

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.

The Role of Glycyrrhizin, an Inhibitor of HMGB1 Protein, in Anticancer Therapy

Certain anticancer drugs, such as the peptide CAMEL (aa sequence KWKLFKKIGAULKVL) induce necrotic type of cell death. During this process, a protein termed high mobility group box 1 (HMGB1) is released from cell nucleus into cytoplasm and then into extracellular milieu. Outside of cells, it becomes a proinflammatory cytokine. Its effects range from stimulation of cancer as well as endothelial cell proliferation, to activation of angiogenesis, cell motility and induction of inflammatory conditions. Release of HMGB1 cytokine during the course of anticancer therapy has negative effects upon the therapy itself, since it leads to tumor relapse. We assumed that the inhibition of HMGB1 activity may be conducive towards better therapeutic results in case of drugs inducing necrotic cell death. In this context we studied glycyrrhizin (GR), a triterpenoid saponin glycoside of glycyrrhizic acid and a well-known inhibitor of HMGB1. We have shown that GR inhibits proliferation and migration of cells stimulated by HMGB1 cytokine, as well as HMGB1-induced formation of blood vessels and reduces inflammatory condition (lowering tumor necrosis factor α levels). GR-mediated inhibition of HMGB1 activity (CAMEL-induced release) impedes, in turn, tumor regrowth in mice. As expected, inhibited tumor regrowth is linked to diminished tumor levels of the released HMGB1 and reduced inflammatory condition. To conclude, the use of GR significantly improved anticancer effectiveness of the CAMEL peptide.

Impact of low frequency pulsed magnetic fields on pain intensity, quality of life and sleep disturbances in patients with painful diabetic polyneuropathy

AIM The aim of this randomized, placebo-controlled, double-blind study was to assess whether a low frequency magnetic field can influence pain intensity, quality of life and sleep, and glycaemic control in patients with painful diabetic polyneuropathy. METHODS Sixty-one patients were randomized into two groups: the study group comprised 32 patients exposed to a low frequency magnetic field, average pain duration 23 months; the control group included 29 patients who received sham exposure, average pain duration 28 months. Patients were exposed for three weeks, 20 min a day, five days a week. The magnetic field generator was a Viofor JPS device (Med & Life, Komorow, Poland). All subjects filled out the following questionnaires five times (at the beginning and after one, two, three and five weeks): SFMPQ-VAS (pain evaluation), EuroQol EQ-5D and MOS Sleep Scale. HbA(1c) was evaluated at baseline and after five weeks. RESULTS Significant reductions in pain intensity were seen in both the study group (visual analogue scale [VAS] value of 73 mm at baseline versus 33 mm after three weeks) and controls (VAS 69 mm at baseline versus 41 mm after three weeks). The extent of pain reduction did not differ significantly between the groups at any time. Also, both groups had similar improvements in EuroQol, MOS and HbA(1c) values. CONCLUSION Genuine magnetic field exposure has no advantage over sham exposure in reducing pain intensity, improving quality of life, and decreasing sleep disturbances and HbA(1c).

Poly[tri(ethylene glycol) ethyl ether methacrylate]-coated surfaces for controlled fibroblasts culturing.

Well-defined thermosensitive poly[tri(ethylene glycol) monoethyl ether methacrylate] (P(TEGMA-EE)) brushes were synthesized on a solid substrate by the surface-initiated atom transfer radical polymerization of TEGMA-EE. The polymerization reaction was initiated by 2-bromo-2-methylpropionate groups immobilized on the surface of the wafers. The changes in the surface composition, morphology, philicity, and thickness that occurred at each step of wafer functionalization confirmed that all surface modification procedures were successful. Both the successful modification of the surface and bonding of the P(TEGMA-EE) layer were confirmed by X-ray photoelectron spectroscopy (XPS) measurements. The thickness of the obtained P(TEGMA-EE) layers increased with increasing polymerization time. The increase of environmental temperature above the cloud point temperature of P(TEGMA-EE) caused the changes of surface philicity. A simultaneous decrease in the polymer layer thickness confirmed the thermosensitive properties of these P(TEGMA-EE) layers. The thermosensitive polymer surfaces obtained were evaluated for the growth and harvesting of human fibroblasts (basic skin cells). At 37 °C, seeded cells adhered to and spread well onto the P(TEGMA-EE)-coated surfaces. A confluent cell sheet was formed within 24 h of cell culture. Lowering the temperature to an optimal value of 17.5 °C (below the cloud point temperature of the polymer, TCP, in cell culture medium) led to the separation of the fibroblast sheet from the polymer layer. These promising results indicate that the surfaces produced may successfully be used as substrate for engineering of skin tissue, especially for delivering cell sheets in the treatment of burns and slow-healing wounds.

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.

Monitoring of whole body cryotherapy effects by thermal imaging: preliminary report

In whole body cryotherapy the whole human body is exposed to low temperature below -100 degrees C in a special room called cryogenic chamber for a very short period of time (2-3 minutes). The impact of cold can cause many different biochemical and physiological reactions of the organism. The skin temperature response due to whole body cryotherapy was studied by means of infrared measurements. The thermograms of chosen body parts of patients suffering from low back pain were performed before and after whole body cooling on the 1(st), 5(th) and the last (10(th)) day of medical treatment. Infrared imaging performed after cold impact owing to the enhancement of the skin temperature profile may reveal a slight decrease of the inflammatory states as a result of the 10 sessions of cryotherapy.