Marcin Frączek

Lactoferrin inhibits the growth of nasal polyp fibroblasts

The aim of this study was to evaluate the effects of lactoferrin (LF) on the growth of fibroblasts derived from nasal polyps. We showed that the proliferation of fibroblasts was inhibited in a dose-dependent manner by both native and recombinant LF. The greatest inhibition of proliferation was caused by human milk-derived, iron-saturated LF. The inhibition of fibroblast proliferation was not species specific because bovine LF also was active. The interaction between LFs and a putative cell receptor did not depend on the sugar composition of the glycan moiety of the LF molecule because lactoferrins of different origins were active and the addition of monosaccharides to the cultures did not block proliferation. However, the treatment of fibroblasts with sodium chlorate (an inhibitor of glycosaminoglycan sulfation) or the addition of heparin abolished the inhibitory effect of LF, suggesting that LF binds heparan sulfate-containing proteoglycans. The significance of LF in nasal excretions in controlling polyp formation is discussed.

Global DNA methylation status in laryngeal cancer

The purpose of our study was to evaluate if DNA methylation level in leukocytes may be used as a surrogate marker of genome methylation status in laryngeal cancer tissues.

Znaczenie prognostyczne ekspresji kwaśnych fosfataz CDC25 w raku krtani

Summary CDC25 phosphatases, significant positive regulators of the cell cycle play a pivotal role in controlling cell proliferation during development and tumorigenesis. The prevalence and clinical implications of CDC25 immunoreactivity in laryngeal squamous cell cancer (LSCC) patients however, have not been elucidated. Aim The object of the study was to assess the relationship between the expression levels of CDC25A, CDC25B and clinicopathological parameters and overall survival time of patients with LSCC. Material and methods Tissue blocks from 46 patients treated surgically at our institution between 1992 and 2000 were available for this study. Immunohistochemistry using polyclonal antibodies against CDC25A and CDC25B was used to examine proteins expression. Ki-67 antigen expression was examined as a cell proliferation marker. Control group consisted of 21 samples of unchanged mucosa. Results CDC25A and CDC25B expression was observed in 96% (44/46) and 56,5% (26/46) of tumors; the mean labeling index was 73,9% and 36,5% respectively. CDC25 phosphatases expression was higher in LSCC compare to the control group (p Conclusions The expression of CDC25A, CDC25B and the proliferation marker Ki-67 are not associated with prognosis in LSCC.UNLABELLEDnCDC25 phosphatases, significant positive regulators of the cell cycle play a pivotal role in controlling cell proliferation during development and tumorigenesis. The prevalence and clinical implications of CDC25 immunoreactivity in laryngeal squamous cell cancer (LSCC) patients however, have not been elucidated.nnnAIMnThe object of the study was to assess the relationship between the expression levels of CDC25A, CDC25B and clinicopathological parameters and overall survival time of patients with LSCC.nnnMATERIAL AND METHODSnTissue blocks from 46 patients treated surgically at our institution between 1992 and 2000 were available for this study. Immunohistochemistry using polyclonal antibodies against CDC25A and CDC25B was used to examine proteins expression. Ki-67 antigen expression was examined as a cell proliferation marker. Control group consisted of 21 samples of unchanged mucosa.nnnRESULTSnCDC25A and CDC25B expression was observed in 96% (44/46) and 56.5% (26/46) of tumors; the mean labeling index was 73.9% and 36.5% respectively. CDC25 phosphatases expression was higher in LSCC compare to the control group (p<0.001). There was not any significant correlation between the levels of CDC25 phosphatases and investigated variables. In univariate analysis, all classical clinicopathological parameters but none of the proteins were related to the overall survival time.nnnCONCLUSIONSnThe expression of CDC25A, CDC25B and the proliferation marker Ki-67 are not associated with prognosis in LSCC.

Zmiany potencjału proliferacyjnego fibroblastów pochodzących z polipów nosowych, w hodowlach in vitro, pod wpływem pochodnych wit. D

INTRODUCTIONnRecurrent polyposis in the same patient resulting in the necessity of repeated surgeries forced to search for new pharmacological therapeutic methods. At present, locally acting glycocorticosteroids have the greatest value in the treatment of nasal polyposis. Polyps grow is connected with inflammation process and proliferation of fibroblasts.nnnOBJECTIVEnAn evaluation of calcitriol and tacalcitol influence on proliferation of fibroblasts extracted from nasal polyps.nnnMATERIALnconsisted of 9 tissue samples coming from nasal polyps sampled during polypectomies. The testing was performed on the polyps fibroblasts after the sixth passage after the primary culture was established. Three days after the culture was started the cells were poured with nutrient medium without serum added and after further 24 hours was replaced by nutrient medium with takalcitol and calcitriol in the defined concentrations. The expression of the genes coding histone H3 was evaluated with the use of RT-PCR technique.nnnRESULTSnTacalcitiol and calcitriol in vitro decrease proliferation of fibroblasts sampled from nasal polyps. Inhibition is most effective for the concentration of 10-4M. Tacalcitiol and calcitriol also inhibit level of histone H3 gene expression.nnnCONCLUSIONnExperimental data suggest tacalcitiol to be more effective in the same concentration. Present studies may indicate the direction of further investigation in the potential pharmacological treatment on nasal polyps.Summary Introduction Recurrent polyposis in the same patient resulting in the necessity of repeated surgeries forced to search for new pharmacological therapeutic methods. At present, locally acting glycocorticosteroids have the greatest value in the treatment of nasal polyposis. Polyps grow is connected with inflammation process and proliferation of fibroblasts. Objective An evaluation of calcitriol and tacalcitol influence on proliferation of fibroblasts extracted from nasal polyps. Material consisted of 9 tissue samples coming from nasal polyps sampled during polypectomies. The testing was performed on the polyps fibroblasts after the sixth passage after the primary culture was established. Three days after the culture was started the cells were poured with nutrient medium without serum added and after further 24 hours was replaced by nutrient medium with takalcitol and calcitriol in the defined concentrations. The expression of the genes coding histone H3 was evaluated with the use of RT-PCR technique. Results Tacalcitiol and calcitriol in vitro decrease proliferation of fibroblasts sampled from nasal polyps. Inhibition is most effective for the concentration of 10-4M. Tacalcitiol and calcitriol also inhibit level of histone H3 gene expression. Conclusion Experimental data suggest tacalcitiol to be more effective in the same concentration. Present studies may indicate the direction of further investigation in the potential pharmacological treatment on nasal polyps.

Zróżnicowanie polipów nosa w badaniach techniką mikromacierzy oligonukleotydowych

UNLABELLEDnNasal polyps, according to many authors, generate as a result of chronic inflammation process with activation of cytokines, immunological reaction mediators that regulate proliferation, differentiation and cell apoptosis. Clarifying molecular mechanisms present in those disturbances may have diagnostic and prognostic value in evaluation of recurrence, dynamics and differentiation of nasal polyps as well as in their therapy.nnnAIMnThe aim of the work was an analysis of nasal polyps on the basis of molecular, histopathological and clinical picture as well as comparing differentiated genes transcription in nasal polyps and proper nasal mucosa.nnnMATERIAL AND METHODnOligonucleotide array with HGU 133A - Affymetrix were used to analyze the expression of 22,283 genes in nasal polyp tissues from 17 patients. The control group consisted of 8 tissue samples from patients after nasal septoplasty surgery.nnnRESULTSnAll the samples could be classified to nasal polyps group or proper mucosa group, it reflected significant differences in genes profile expression in both groups. The evaluation of 22,283 genes transcriptions showed that in most cases nasal polyps tissue reflect classification connected with dominant inflammation cells infiltration. The data obtained let distinguish subgroups connected with clinical condition of the patients. The subgroup with massive nasal and sinus polyposis, eosinophilia and differentiated lower respiratory airways hyperactivity and the subgroup without eosinophilia infiltration may be distinguished. The data obtained suggest that molecular mechanisms may influence on the promotion and kind of inflammation process as well as the clinical course of nasal polyps.Summary Nasal polyps, according to many authors, generate as a result of chronic inflammation process with activation of cytokines, immunological reaction mediators that regulate proliferation, differentiation and cell apoptosis. Clarifying molecular mechanisms present in those disturbances may have diagnostic and prognostic value in evaluation of recurrence, dynamics and differentiation of nasal polyps as well as in their therapy. Aim The aim of the work was an analysis of nasal polyps on the basis of molecular, histopathological and clinical picture as well as comparing differentiated genes transcription in nasal polyps and proper nasal mucosa. Material and method Oligonucleotide array with HGU 133A – Affymetrix were used to analyze the expression of 22 283 genes in nasal polyp tissues from 17 patients. The control group consisted of 8 tissue samples from patients after nasal septoplasty surgery. Results All the samples could be classified to nasal polyps group or proper mucosa group, it reflected significant differences in genes profile expression in both groups. The evaluation of 22 283 genes transcriptions showed that in most cases nasal polyps tissue reflect classification connected with dominant inflammation cells infiltration. The data obtained let distinguish subgroups connected with clinical condition of the patients. The subgroup with massive nasal and sinus polyposis, eosinophilia and differentiated lower respiratory airways hyperactivity and the subgroup without eosinophilia infiltration may be distinguished. The data obtained suggest that molecular mechanisms may influence on the promotion and kind of inflammation process as well as the clinical course of nasal polyps.

Posocznica u pacjentki z zapaleniem zatoki klinowej

Summary Introduction We present a case of sepsis caused by isolated sphenoiditis. Material and method The case being described concerns 61-year-old woman treated at the Department of Occupational Diseases of Wroclaw Medical University due to body temperature maintaining for 2 months at above 38°C, leucocytosis reaching 14–16 thousand and weight loss of about 4 kg. Detailed diagnostics did not confirm the preliminary diagnosis of system or neoplastic disease. Bacteriological blood examination revealed the presence of staphylococcus aureus susceptible to Vancomycin and Tienam. The attempt of pharmacological treatment did not produce the expected effect. NMR examination of the facial skeleton proved partial shadowing of the Sphenoidal sinus. The patient was admitted for surgical treatment. After the sphenoidal sinus was cut open, mucopurulent contents was found inside. During microbiological examination, staphylococcus aureus with identical susceptibility was cultured from the mucopurulent contents. After 3-week guided antibiotic therapy, permanent temperature regression and permanent improvement of the patients condition were achieved. Results Surgical treatment combined with intensive antibiotic therapy caused the complete regression of symptoms. Conclusion Isolated sphenoiditis occurs rarely but it still is a serious diagnostic and therapeutic problem. Diagnosis delay and disease progress may lead to life-threatening complications.

Reliability of computed tomography scans in the diagnosis of chronic rhinosinusitis

BACKGROUNDnParanasal computed tomography (CT) has become the investigation method of choice to confirm or exclude the diagnosis of chronic rhinosinusitis (CRS) on the basis of its ability to deliver objective data regarding the presence of inflamed mucosa or polyps.nnnOBJECTIVESnThe aim of the study was to assess the reliability of CT scan findings among untreated CRS patients without the presence of polyps in a nasal endoscopy.nnnMATERIAL AND METHODSnAmong patients with clinically demonstrated CRS considered for surgery, 93 subjects who had had 2 CT scans performed at different time points in the diagnostic process were enrolled into the study. Paranasal sinus involvement on both CT scans was scored using the Lund-Mackay (L-M) and modified Lund-Mackay scales. Both CT exams served to assess the extent of the potential endoscopic sinus surgery.nnnRESULTSnThe time interval between CT scans ranged from 31 to 1,162 days (mean: 338 days). The L-M scores from the 1st CT examination correlated statistically with the results of the 2nd CT (r = 0.86; p < 0.05). When compared to the 1st scan, the L-M score in the 2nd CT scan remained the same in 36 patients (39%), increased in 23 patients (25%) and decreased in 34 patients (36%). There was no statistically significant correlation between the change in the L-M scores and the time interval between CT examinations.nnnCONCLUSIONSnThe present study indicates that mucosal thickening within paranasal sinuses among untreated patients with CRS is stable over shortand middle-time intervals, regardless of the initial intensity of the disease. The time delay between the CT examination and qualification for surgery does not influence the decision regarding the performance of the operation. The results suggest the conclusion that repeating CT scans in symptomatic, untreated patients with CRS should be seriously considered.

Ocena związku pomiędzy ekspresją receptora dla naskórkowego czynnika wzrostu (EGFR) i białka p53 a promieniowrażliwością raka krtani

UNLABELLEDnRadiotherapy and surgery are the most important treatment modalities for the majority of laryngeal cancers. Because of high efficacy and better organ preservation radiotherapy is generally preferred for early and intermediate stage of the disease. Some of patients with more locally advanced cancers can still be cured by means of radiotherapy, but we have not got reliable prognostics factors for predicting radiocurability. THE AIM OF MY STUDY: was to investigate the value of p53 and EGFR expression for predicting clinical outcomes of laryngeal cancer patients treated with radiotherapy.nnnMETHODS AND MATERIALSnThe study included 50 patients with laryngeal cancer treated in Department of Radiotherapy of Silesian Oncology Center between the years 1998 and 2003. Paraffin sections from archival material were studied immunohistochemically for detection p53 and EGFR and correlated with clinical parameters and local tumor control and patient survival.nnnRESULTSnAccumulation of p53 and EGFR were detected in 65% and 50% of tumor respectively. No relationship was observed between immunostaining for investigated proteins and clinicopathologic factors. The TNM tumor stage was the most significant prognostic factor for local control and overall survival. p53 was favorable prognostic factor with 5-years disease free survival rate 82% for patients p53-positive and 75% for p53-negative patients (p = 0.04).nnnCONCLUSIONnThe TNM tumor stage is the most important prognostic factor for laryngeal cancer. Tumors accumulating p53 have better prognosis what indicates possibly role for p53 immunohistochemical analysis for predicting outcomes of radiotherapy in patients with laryngeal cancer.

Znaczenie prognostyczne ekspresji cykliny D1 i cykliny B u pacjentów z rakiem krtani leczonych radioterapią

Summary Cyclin B1 and cyclin D1 playing the role of regulatory subunits of cyclin-dependent kinases responsible for progression of cell cycle are involved in carcinogenesis of head and neck tumors. The aim of this study is to investigate their value for predicting clinical outcome after radiotherapy of laryngeal squamous cell cancer (LSCC). Material and methods The study included 50 patients with LSCC treated between the years 1998 and 2003 with radiotherapy. Tissue samples were studied immunohistochemically for detection of cyclin B1 and cyclin D1 and their expression were correlated with clinicopathological factors, local tumor control and patient survival. Results Accumulation of cyclin D1 and cyclin B1 were detected in 36% and 48% of tumors respectively. No relationship was observed between immunostaining for analyzed proteins and clinicopathologic factors. Cyclin B1 overexpression was associated with higher rate of locoregional recurrence. Five-year disease free survival rate for patients with cyclin B1 positive tumors was 73% v. 84% for cyclin B1 negative patients (p = 0,005). Conclusion The expression of cyclin D1 in LSCC does not seem to have a prognostic significance. Overexpression of cyclin B1 may be an indicator of the risk of locoregional recurrence in patient receiving radiotherapy. Thus cyclin B1 detected by immunohistochemistry can be useful for predicting outcome of radiotherapy in patients with LSCC.