Concurrent Squamous Cell Carcinoma and Leiomyosarcoma in the Larynx at Relapse 15 Years Post-radiation for Primary Laryngeal Cancer.

Malignant tumours of the larynx account for 50% of all head and neck neoplasms. Squamous cell carcinoma is the most common malignancy of the larynx and accounts for 95-98%. Leiomyosarcoma (LMS) originating in larynx is a very rare malignant tumour derived from the smooth muscle tissue. The authors present a case of a 75-year man with coexistent squamous cell carcinoma and leiomyosarcoma in the larynx 15 years after radiation therapy for promany laryngeal cancer. Two cases of the synchronous presence of these neoplasms have been reported so far in English literature. This paper presents the clinical picture, radiological and histopathological diagnoses, and treatment of this case. Key Words: Squamous cell carcinoma, Leiomyosarcoma, Larynx.

Anatomical and Clinical Implications in Neocondyle Stability After a Condylectomy.

: A condylectomy of the mandibular condyle is considered to be the treatment of choice in most cases of condylar head hyperactivity. The aim of the procedure is to remove the growth center of the mandible which is responsible for the mandibular enlargement and asymmetry. This surgical procedure has an impact on the condyle shape and position, but the restoration of mandibular movement and a stable joint position (namely, the proper alignment of the newly shaped condylar head within the condyle fossa) should also be considered important surgical outcomes. In this article, the authors present their own experience in performing condylectomies with an arthroplasty procedure and a special forced suturing technique (FST) in terms of achieving early, accurate mandibular movement and maintaining a stable condyle position in early and late outcomes. MATERIALS AND METHODS: A modified high condylectomy with arthroplasty and FST results had been studied in anatomical, radiological, and clinical model. RESULTS: Early findings after FST are promising. A slight improvement in lateral jaw movement was noted after condylectomy with arthroplasty (P < 0.05) both in early and late follow-up. Incisal opening, mandibular protrusion, and lateral movement were sustained. A stable condyle position within the fossa was achieved in each case of condylectomy with arthroplasty (P < 0.05). CONCLUSIONS: The FST condylectomy and reattachment of the lateral pterygoid muscle in a new, wider position provided an improvement in lateral jaw movement as well as in incisal opening and mandibular protrusion in early follow-up examination compared to the presurgical values. It seems that the FST enabled a better new condylar head position in the glenoid fossa and improved early functional mandibular movement.

[A case of rare laryngeal neurogenic tumor].

Laryngeal schwannoma is a rare benign tumour of the larynx. Schwannomas derive from the Schwann cells. Magnetic resonance imaging (MRI) is the best imaging tool for suggesting the diagnosis. We report case of laryngeal schwannoma. The case was a 61-year-old man with a 1-year history of dysphonia and stridor. Laryngoscopy revealed a submucosal mass of the glottic area. A computed tomography scan of the larynx showed an 26(CC) x 18 (TR) x 24 (AP)mm expansile mass in the glottic area. Histopathological examination diagnosed a schwannoma of the larynx. External surgeries were successfully performed. Diagnosis and specific treatment are discussed.

Reliability of computed tomography scans in the diagnosis of chronic rhinosinusitis.

BACKGROUND: Paranasal 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. OBJECTIVES: The 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. MATERIAL AND METHODS: Among 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. RESULTS: The 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. CONCLUSIONS: The 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.

Investigation of sinonasal anatomy via low-dose multidetector CT examination in chronic rhinosinusitis patients with higher risk for perioperative complications.

The aim of the study was to compare visualisation of the surgically relevant anatomical structures via low- and standard-dose multidetector CT protocol in patients with chronic rhinosinusitis (CRS) and higher risk for perioperative complications (i.e. presence of bronchial asthma, history of sinus surgery and advanced nasal polyposis). 135 adult CRS patients were divided randomly into standard-dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). The detectability of the vital anatomical structures (anterior ethmoid artery, optic nerve, cribriform plate and lamina papyracea) was scored using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon. Polyp sizes were quantified endoscopically according to the Lildholdt's scale (LS). Olfactory function was tested with the "Sniffin' Sticks" test. On the low-dose CT images, detectability ranged from 2.42 (better than poor) for cribriform plate among anosmic cases to 4.11 (better than good) for lamina papyracea in cases without nasal polyps. Identification of lamina papyracea on low-dose scans was significantly worse in each group and the same was the case with cribriform plates in patients with advanced polyposis and anosmia. Cribriform plates were the most poorly identified (between poor and average) among all the structures on low-dose images. Identification of anterior ethmoid artery (AEA) with reduced dose was insignificantly worse than with standard-dose examination. The AEA was scored as an average-defined structure and was the second weakest visualised. In conclusion, preoperatively, low-dose protocols may not sufficiently visualise the surgically relevant anatomical structures in patients with CRS and bronchial asthma, advanced nasal polyps (LS > 2) and history of sinus surgery. Low mAs value enables comparable detectability of sinonasal landmarks with standard-dose protocols in patients without analysed risk factors. In the context of planned surgery, the current preferences of the tube should be carefully evaluated for different patient constitutions to minimise the risk of complications.

The usefulness of free dicom viewers in rhinologic practice.

Indroduction: The planning of the course of surgery in patients with paranasal sinus disorders requires the meticulous evaluation of computed tomography (CT) scans. However, ENT doctors still often receive unsatisfactory DICOM images, which require multiplanar reconstruction (MPR). THE AIM: The objective of the present study was to evaluate and test DICOM viewers with MPR function currently available on the Internet for free. MATERIAL AND METHODS: Detailed Internet searches and analysis of databases were carried out to find the maximum number of browsers. Available software was downloaded to assess, qualitatively and quantitatively, the parameters and functions useful in rhinologic practice. Additionally, a questionnaire was developed in order to ascertain the expectations and habits of ENT doctors in relation to DICOM browsers and CT scan evaluation. RESULTS AND CONCLUSIONS: Among the hundreds of browsers, 17 programs were chosen to be included in the final comparison. The outcomes of the survey proved that many free DICOM tools are effective alternatives to commercially available programs. However, the results do not enable us to predict precisely which tool will meet the needs of each physician. The survey among ENT doctors highlighted their limited awareness of software with MPR functions, in particular those that scored best in the test.

Nasal endoscopy: an adjunct to patient selection for preoperative low-dose CT examination in chronic rhinosinusitis.

OBJECTIVES: The growing awareness of increased X-ray exposure to the public has led to the propagation of several methods for reducing the radiation dose during CT examination. Low-dose CT protocols do not, however, have an established role in pre-operative evaluation. The aim of this article was to assess the usefulness of nasal endoscopy in the selection of patients under pre-operative care for low-dose CT examination. METHODS: A cadaver head was used to discover institutional minimum acceptable CT image quality and scanning settings. Then, 134 adult patients with chronic rhinosinusitis (CRS) were enrolled into the study and divided randomly into standard dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). Subjective assessment of the diagnostic image quality of the surgically relevant anatomical structures was compared using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon independently. Pathologic states of the nose were quantified according to the Lund-Kennedy endoscopic system (LKES) and Lildholdt's scale. RESULTS: Image quality was similar in low-dose and standard dose groups in patients without polyps. The quality of 13% of scans from patients with polyps from the low-dose group and 4% from the standard dose group was in the range from moderate to poor. The quality of scans obtained with low milliamperes second (mAs) values worsened in patients with polyps in the middle meatus, but the difference was particularly pronounced compared with standard dose among subjects with Lildholdt's score above 2 (p < 0.001). Correlation with LKES revealed that changes other than polyps (i.e. discharge, oedema, scaring or crusting) in the nasal cavity alone do not affect the image quality. Interobserver agreement in both groups was very high. CONCLUSIONS: Low-dose scanning should be promoted as the screening imaging method of choice in patients with suspected CRS. Furthermore, low mAs value examination can be performed pre-operatively without fear of significant image quality deterioration in uncomplicated CRS patients without polyps, or with minor changes in nasal endoscopy. Standard dose CT, which provides a better identification of bony landmarks, minimizes diagnostic errors and risk to patients, so it might be considered in those with polyps below the middle turbinate.

Coexistent chronic myelogenous leukemia with squamous cell carcinoma of the larynx associated with NOD2/CARD15 mutation in a young adult.

We report the case of a 37-year-old man with human papillomavirus-positive squamous cell carcinoma of the larynx coexisting with chronic myelogenous leukemia. The patient had no history of smoking or alcohol consumption. Within a few months, his rapidly growing tumor was classified as T4aN2cM0. It could be assumed that the rapid increase in the tumor mass, which did not respond positively to treatment, might have been associated with the coexistence of the chronic myelogenous leukemia, which had been found incidentally. Genetic testing revealed the presence of insertion mutation 3020insC within the NOD2 gene, which might be an important genetic predisposing factor, not only for a single tumor such as laryngeal cancer, but also for multiple primary neoplasms. The presence of an NOD2 mutation could significantly worsen the course of the cancer. Therefore, given the relatively high frequency of 3020insC mutations in the general population, it might be reasonable to perform genetic testing on a wider scale for patients with head or neck cancer, particularly in cases that follow an atypical course. It is also worth emphasizing the importance of thorough and periodically repeated laryngeal examinations in patients with chronic leukemia.

The usefulness of free dicom viewers in rhinologic practice.

Indroduction: The planning of the course of surgery in patients with paranasal sinus disorders requires the meticulous evaluation of computed tomography (CT) scans. However, ENT doctors still often receive unsatisfactory DICOM images, which require multiplanar reconstruction (MPR). THE AIM: The objective of the present study was to evaluate and test DICOM viewers with MPR function currently available on the Internet for free. MATERIAL AND METHODS: Detailed Internet searches and analysis of databases were carried out to find the maximum number of browsers. Available software was downloaded to assess, qualitatively and quantitatively, the parameters and functions useful in rhinologic practice. Additionally, a questionnaire was developed in order to ascertain the expectations and habits of ENT doctors in relation to DICOM browsers and CT scan evaluation. RESULTS AND CONCLUSIONS: Among the hundreds of browsers, 17 programs were chosen to be included in the final comparison. The outcomes of the survey proved that many free DICOM tools are effective alternatives to commercially available programs. However, the results do not enable us to predict precisely which tool will meet the needs of each physician. The survey among ENT doctors highlighted their limited awareness of software with MPR functions, in particular those that scored best in the test.

IMPACT OF GENISTEIN AND PHYTIC ACID ON THE VIABILITY AND PROLIFERATION ACTIVITY OF NASAL POLYPS' CELLS IN AN IN VITRO MODEL.

In developed countries, chronic rhinosinusitis with nasal polyps is one of the diseases that diminish patients' quality of life most significantly. Treatment of that often incurable disease is based on the steroids and surgery in patients who had failed thorough conservative management. It appears that the introduction of new treatment agents suppressing inflammation process and inhibiting cells' proliferation would be a valuable therapeutic option. The aim of the present study was to evaluate the in vitro effect of genistein and phytic acid on the viability and growth rate of fibroblasts derived from nasal polyps. Cells were incubated with various concentrations of genistein (5-500 µM) and phytic acid (100-20,000 µM). After 72 h incubation, cells survivability and cells' growth rate were estimated by combination of WST-1 and LDH methods. QRT-PCR technique was used to determine the expression of histone H3, BCL-2, BAX and P53 genes. Caspase-8 and -9 expressions were evaluated by ELISA assay. Genistein and phytic acid significantly and in dose-specific manner decreased nasal polyps fibroblasts survivability and growth rate. Both agents in similar way decreased cell proliferation as measured by the expression of histone H3. They induce apoptotic machinery by modulating the expression of BCL-2, BAX and caspase-8 activity. Genistein and phytic acid have significant potential for a therapeutic role in the treatment of chronic rhinosinusitis.

ANTIPROLIFERATIVE AND CYTOTOXIC EFFECT OF SELECTED VITAMIN D ANALOGS ON NASAL POLYPS FIBROBLASTS AND OTHER CELLS WITH HIGHER PROLIFERATIVE POTENTIAL.

Besides well-known effect on bone and mineral metabolism vitamin D is involved in essential non-calcemic regulatory mechanisms, such as cellular proliferation, differentiation and apoptosis in various cell types. Major limitation for therapeutic use of calcitriol, a hormonally active form of vitamin D, is its calcemic and phosphatemic action. Recently, more selective vitamin D analogs which retain clinically useful activities with reduced toxicity have been designed. The aim of the present study was to evaluate the in vitro effect of vitamin D analogs on proliferation rate and survivability of cells with increased proliferative activity. The effect of calcitriol, PRI-2191, PRI-1890, PRI-1906 and PRI-2205 was examined. The experiments were performed on cultures derived from nasal polyps and cancer cells lines (SNB-19, C32 and SH-4). Cultures were incubated 72 h with tested compounds, each at the concentration of 0.025, 0.25, 2.5 and 25 µg/mL. The cytotoxic effect of vitamin D analogs and their influence on growth rate were determined using WST-1 assay. RT-QPCR technique was used to evaluate the expression of anti-apoptotic BCL-2 and pro-apoptotic BAX gene. Each of the tested compounds presented significant effect at the concentrations above 0.25 µg/mL. The strongest inhibition of the growth rate and decrease in cell survivability was observed after treatment with PRI-1890 and PRI-2191. Stimulation with calcitriol and other vitamin D analogs led to decrease BCL-2/BAX mRNA ratio in each cell lines. The apparent pro-apoptotic action revealed PRI-2191 followed by PRI-1890. It might be hypothesized that vitamin D analogs supplementation may provide therapeutic benefits not only in oncological patients but also in chronic rhinosinusitis.

[Bilateral squamous carcinoma of the external auditory canal--a case report]. / Obustronny rak plaskonablonkowy przewodu sluchowego zewnetrznego--opis przypadku.

Squamous cell carcinoma of the external auditory canal is a very rare and unusual malignancy, representing less than 0.2% of all head and neck cancers. The authors present a case of 78-year-old patient with bilateral squamous cell carcinoma of the external auditory canal-cT4N0M0 G2, pT4N2bM0, initially treated as a chronic otitis external. The patient was qualifies for the one-step removal of cancer of the earlobe and the external auditory canal. Because of complications during the operation, the plan of treatment was changed. The patient is under oncological control for 13 months.

Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa.

Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosawere analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific-probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in HNC. In HNC of oral cavity only one family of EDC genes (S100 proteins) showed significant cancer-related differences. A number of other transcripts which showed altered expression in HNC require further validation.

Global DNA methylation status in laryngeal cancer.

BACKGROUND: 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. METHODS: We evaluated global DNA methylation using an ultra performance liquid chromatography (UPLC)-based method to assess the total content of 5-methylcytosine (5 mC). RESULTS: The study was performed on DNA isolated from cancer tissues, adjacent normal tissues, and peripheral blood leukocytes in a group of 72 patients with laryngeal cancer. DNA hypomethylation was found in tumor tissue (56%) and normal tissue (49%). There was a significant correlation between the levels of 5 mC in these 2 types of tissue. There was no significant DNA hypomethylation in blood. A negative correlation between tumor grade and blood levels of 5 mC was found. CONCLUSION: The level of leukocyte DNA methylation measured using total 5 mC content cannot be used as a surrogate marker for genome methylation status in laryngeal cancer tissues.

Microarray analysis of NF-κB-dependent genes in chronic rhinosinusitis with nasal polyps.

BACKGROUND: The inflammatory process underlying nasal polyposis is induced and perpetuated by the enhanced activity of several agents including transcription factors. It has recently been demonstrated that one of them, named nuclear factor-kappa B (NF-κB), is implicated in the regulation of multiple pro-inflammatory genes. OBJECTIVES: The aim of the study was to identify using microarray technology which NF-κB-dependent genes are activated in nasal polyp (NP) samples compared to the control mucosa. MATERIAL AND METHODS: The transcriptional activity of genes was analyzed using an oligonucleotide microarray on 15 NPs and 8 cases of normal nasal mucosa. RESULTS: Gene expression patterns obtained in NPs were significantly different from those in normal mucosa. NPs and control cases clustered separately, each of them with large homogeneity in gene expression. Among 582 human NF-κB-dependent genes 25 showed a significantly higher expression in NPs compared to the control. The largest increase focused on gene encoding TFF3 (a 5-fold higher expression) followed by NOS2A (5x), SERPINA1 (4x), UCP2 (4x), OXTR (4x) and IL8 (3x) (p<0.05). In healthy mucosa 19 genes presented increased transcription activity compared to NPs. The most significantly enhanced levels were shown LTF gene (20 fold) followed by KRT6B (7x), LYZ (7x), SD11B2 (5x) and MMP3 (4x) (p<0.05). CONCLUSIONS: DNA microarray technology highlights the involvement of many unsuspected pathologic pathways which could be involved in NP growth. The identification of novel disease-related genes may help to understand the biology of NPs and elaborate new targeted therapy.

A microarray study of gene expression profiles in nasal polyps.

OBJECTIVE: Nasal polyposis (NP) is a multifactorial disease manifesting in chronic inflammation of upper respiratory tract of unknown etiology. We studied mRNA gene expression profiles in NP compared with normal mucosa as well as pointed at genes characteristic of different expression in examined tissues. MATERIAL AND METHODS: Fifty-three patients with NP (36 eosinophilic and 17 neutrophilic NP) were included into the study. Transcriptional activity of genes was analyzed using oligonucleotide microarray in 17 NP and 8 cases of normal nasal mucosa. A study of mRNA expression of selected genes was performed using QRT-PCR. RESULTS: We identified 556 genes, which were differentially expressed between the studied and the control group. Among them 217 showed significantly higher expression, whereas 339 lower expression in NP than in controls. The microarray and QRT-PCR results were compatible for 7 of 8 evaluated genes. In NP strongly significant higher transcriptional activity of MMP10, NOS2A, ALOX15 and IL-8 genes was observed. In the control group, significantly higher expression of DMBT1, ALOX12 and LTF genes was detected. CONCLUSION: The analysis of gene expression in inflammatory changed nasal polyp tissues may become a supplementary method in diagnostics and treatment. Molecular alterations may indicate changes during the clinical course of the disease.

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.

[Relation between epidermal growth factor receptor (EGFR) and p53 expression and radiocurability of laryngeal squamous cell cancer]. / Ocena zwiazku pomiedzy ekspresja receptora dla naskórkowego czynnika wzrostu (EGFR) i bialka p53 a promieniowrazliwscia raka krtani.

UNLABELLED: Radiotherapy 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. METHODS AND MATERIALS: The 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. RESULTS: Accumulation 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). CONCLUSION: The 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.

[Prognostic significance of cyclin D1 and cyclin B expression in laryngeal squamous cell carcinomas treated with radiotherapy]. / Znaczenie prognostyczne ekspresji cykliny D1 i cykliny B u pacjentów z rakiem krtani leczonych radioterapia.

UNLABELLED: 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.

Influence of vitamin D(3) analogues in combination with budesonid R on proliferation of nasal polyp fibroblasts.

UNLABELLED: Vitamin D (VD) and its different analogues, besides their classic role as regulators of calcium and phosphor homeostasis, have emerged as a large family of antiproliferative agents. Such properties suggested VD potential as a therapy for chronic inflammatory diseases, including nasal polyposis (NP). NP growth involves both an inflammatory process and the proliferation of fibroblast as an important factor inducing aberrations in the phenotype of the epithelium. The aim of this study was to investigate the possible influence of 1alpha,25-dihydroxyvitamin D(3) (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D(3) (tacalcitol) in monotherapy and in combination with budesonid R (BR) on NP fibroblast proliferation. MATERIAL AND METHODS: The study involved 26 samples of NP. NP cells were cultured on 96-well plates beginning with a concentration of 5 x 10(3) cells per well with RPMI 1640 medium supplemented with antibiotics and 10% foetal bovine serum. After the fourth to sixth passage the medium was replaced with a nutrient medium with calcitriol or tacalcitol in a defined concentration (from 10(-9) M to 10(-3) M) alone or in combination with BR in 1:1, 1:3 or 3:1 ratios, each at concentrations from 10(-5) M to 10(-3) M. RESULTS: Growth inhibition of nasal fibroblasts exposed to calcitriol or tacalcitol was noted. Significant antiproliferating activity was observed at calcitriol concentrations of 10(-4) M and 10(-3) M after 48 h, and at a concentration of 10(-3) M after 72 h with the percentage of proliferating cells reduced to 30% compared to the control samples (P < 0.05). In cells treated with tacalcitol the maximal effect was seen at 10(-4) M after 48 h and at 10(-3)M after 72 h with a 60% inhibition with respect to the control (P < 0.05). The inhibition of fibroblast proliferation reached the maximal level when they were exposed to calcitriol: BR (1 : 1) or tacalcitol: BR (1 : 1), each at a concentration of 10(-4) M, after 72 h (82% and 69%, respectively). CONCLUSIONS: The antiproliferative activity of calcitriol and tacalcitol in NP cultures was confirmed. Because of its lower toxicity and higher activity tacalcitol seems to be the more promising agent in NP therapy, both as a single medication and in treatment protocols with BR.