Mariusz Adamek

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.

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).

Combined treatment of urinary bladder cancer with the use of photodynamic therapy (PDT) and subsequent BCG-therapy: a pilot study

INTRODUCTION Transitional cell carcinoma (TCC) of the urinary bladder is nowadays one of the most common cancers in young men. Similarly to other cancers TCC can be treated with curative intent when it is diagnosed very early. In recent years there has been an intensive development of treatment methods of urological diseases based on modern scientific discoveries, one of which is photodynamic therapy (PDT). This treatment in urology may be used either for pre-cancerous lesions, carcinoma in situ or for superficial tumours. PATIENTS AND METHODS In this study, patients were subjected to PDT with subsequent BCG-therapy. In our study we demonstrate cases of 14 patients, who were under observation for minimum 24 months. All patients were diagnosed as having TCC in pathological stage pT1N0M0 (clinical: T1NxM0). They had previously undergone transurethral resection of bladder tumour (TUR-BT) and no exophytic tumours were observed. Patients were instillated intravesically with 4.5g of ALA (aminolevulinic acid) in buffered solution in the bladder for 2h. Afterwards, within 2h the bladder was irradiated with 635nm an argon-pumped dye laser light. Light power on the tip of the fibre was 1.0W. The total energy dose was 2000J equally divided into two to three sessions. RESULTS After 24-month observation total response was observed in eight patients (in histopathological examination urocystitis was diagnosed), partial response (low- or high-grade dysplasia in microscopic examination) in two patients and no response in four patients (cancer cells in excised specimens). CONCLUSIONS :

Fluorescent diagnosis of urinary bladder cancer-—a comparison of two diagnostic modalities

UNLABELLED White light cystoscopy (WLC) is considered to be a standard examination for localisation and surveillance of transitional cell cancer of urinary bladder. However, in patients who have undergone transurethral resection of bladder tumour (TUR-BT) sensitivity of this method is too low for early detection of cancer recurrence. In order to improve this unsatisfactory situation new diagnostic procedures are still under investigation. Fluorescent diagnosis is a modern diagnostic option based on the detection of distinctive fluorescence of normal and pathological tissue. Currently two techniques are in clinical use: autofluorescent diagnosis, also termed laser-induced fluorescence (LIF) and photodynamic diagnosis (PDD). In this study we have analysed sensitivity and specificity of the fluorescent diagnosis to validate the best mode of bladder cancer diagnosis. A total of 281 patients, after electroresection of bladder tumour due to transitional cell carcinoma, without any signs of tumour recurrence in white-light cystoscopy, were divided in two groups: 52 patients underwent PDD and in 229 patients autofluorescent diagnosis was performed. Bladder washings and excisions from suspicious red fluorescent spots were taken for histopathological and cytological analyses. Sensitivity and specificity of PDD equalled to 90.91 and 66.60%, respectively. In case of autofluorescence diagnosis these values amounted to: 97.83 and 70.07%, respectively. The overall sensitivity and specificity of fluorescent examination equalled to 96.49 and 69.46%, respectively. CONCLUSION Autofluorescence diagnosis (LIF) of pathological lesions within urinary bladder has been proven to be more sensitive than PDD as evaluated by a non-parametrical test for structure indicators comparison (LIF versus PDD, P=0.0056).

Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect

ABSTRACT The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis—even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed. This can be achieved using PDK inhibitors, such as dichloroacetate. Patients suffering from ischemic conditions might benefit from this effect. On the other hand, the β-blockers (adrenergic β-antagonists) often used in these patients appear to improve cancer-specific survival, and nonselective β-blockers have been shown to promote glucose oxidation. Might there be a link?

Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma

It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF‐7 cells was carried out. Dietary administered CLO caused the dose‐dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl‐2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase‐3 and ALDH1 expression increase after high‐dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro‐apoptotic effects of CLO extract in MCF‐7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase‐7, Bcl‐2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.

Angiomodulators in cancer therapy: New perspectives

The formation of new blood vessels plays a crucial for the development and progression of pathophysiological changes associated with a variety of disorders, including carcinogenesis. Angiogenesis inhibitors (anti-angiogenics) are an important part of treatment for some types of cancer. Some natural products isolated from marine invertebrates have revealed antiangiogenic activities, which are diverse in structure and mechanisms of action. Many preclinical studies have generated new models for further modification and optimization of anti-angiogenic substances, and new information for mechanistic studies and new anti-cancer drug candidates for clinical practice. Moreover, in the last decade it has become apparent that galectins are important regulators of tumor angiogenesis, as well as microRNA. MicroRNAs have been validated to modulate endothelial cell migration or endothelial tube organization. In the present review we summarize the current knowledge regarding the role of marine-derived natural products, galectins and microRNAs in tumor angiogenesis.

Circulating concentration of markers of angiogenic activity in patients with sarcoidosis and idiopathic pulmonary fibrosis

BackgroundAngiogenesis is an important process involved in the pathogenesis of diffuse parenchymal lung diseases. The aim of the study was to compare the angiogenic profile of patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF) based on analysis of circulating factors.MethodsSerum concentrations of angiopoietin-2 (Ang-2), follistatin, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-8 (IL-8), platelet derived growth factor-BB (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1) and vascular endothelial growth factors (VEGF) were measured in the patients and the healthy subjects.ResultsSerum concentrations of G-CSF, follistatin, PECAM-1 and IL-8 were significantly higher in the IPF patients in comparison with the control group and the sarcoid patients. PDGF-BB concentrations were also significantly higher in serum of IPF patients than in sarcoid patients, but not than in the controls. In contrast, Ang-2 and VEGF concentrations did not differ significantly between the three groups. In the sarcoid patients, irrespective of the disease activity or the radiological stage, serum concentrations of these cytokines were similar to the control group.ConclusionsThese results indicate that differences may exist in angiogenic activity between patients with parenchymal lung diseases. In contrast to sarcoidosis, IPF is characterized by a higher serum concentration of different molecules involved in the angiogenic processes .