Biomedical subjects

Jan Betka

Publications and source records attributed to Jan Betka.

15 recordsLinked to original sources

PubMed2005

Glycobiology of head and neck squamous epithelia and carcinomas.

An impressive variety of regulatory processes including cell adhesion and migration, proliferation, apoptosis and differentiation folding and routing of glycoproteins have been found to be mediated by specific lectin-carbohydrate interactions. This article summarizes the data on glycobiological aspects of differentiation of squamous epithelia in the head and neck region under physiological conditions and in cancer. The possible function of lectins in tumor development and invasiveness is debated. Introduction of labeled endogenous lectins as a tool for the study of functional glycomics at the cellular level in head and neck squamous epithelia and carcinomas enables a complex interpretation of studied data because these lectins are normally occurring in these tissues. The lectinology of Langerhans cells in head and neck squamous epithelia and carcinoma is also mentioned. Finally, the use of the described data in the diagnosis and prospectively in the treatment of head and neck squamous cell carcinoma is shown.

Carbohydrate Metabolism↗

PubMed2005

Correlation of expression of nuclear proteins pKi67 and p63 with lectin histochemical features in head and neck squamous cell cancer.

This study represents a combined lectin and immuno-histochemical analysis of normal, dysplastic and malignant squamous epithelia of the upper aerodigestive tract with emphasis on the relation between lectin reactivity and the cells' proliferative/anti-apoptotic potential. Staining by double-labeling to detect pKi67, DeltaNp63alpha, alpha2,3/6-linked sialic acid (NeuNAc) and galectin-3-reactive epitopes was performed on specimens of 8 normal cases, 27 primary tumours and 15 regional lymph node metastases. Normal epithelia expressed alpha2,6-linked NeuNAc in the basal layer, while alpha2,3-linked NeuNAc was observed in suprabasal layers. In normal epithelium pKi67 and DeltaNp63alpha positivity was seen in the basal layer and galectin-3-reactive sites in suprabasal layers. The studied squamous cell carcinomas and their metastases showed a tendency for stratification but with markedly altered architecture. The expression of the studied markers was heterogeneous between the different cancer cases but comparable between the corresponding primary and secondary lesions. Glycophenotypic properties were correlated with the level of differentiation. Tumour cell populations were characterized by occurrence of the p63+/pKi67+ alpha2,3-NeuNAc+ alpha2,6-NeuNAc+ phenotype. Analysis of the expression patterns of pKi67, p63 and galectin-3-reactive epitopes (Gal-3-RE) delineated statistically significant interrelationships (Gal-3-RE vs. p63: r = -0.709; Gal-3-RE vs. pKi67: r = -0.623; pKi67 vs. p63: r = 0.895). Of the studied markers only Gal-3-RE expression was correlated to the differentiation-dependent grading (G1 vs. G2: p = 0.007, G2 vs. G3: p = 0.006, G1 vs. G3: p = 0.002). DeltaNp63alpha expression was statistically different only between G1 and G3 (p = 0.03). No statistically significant differences were detected between the primary tumours and the corresponding regional lymph node metastases. Based on the concept of the sugar code further analysis of cell characteristics such as proliferation together with lectin histochemical features, especially using tissue lectins as probes, is thus warranted.

Carcinoma, Squamous Cell↗

PubMed2004

Galectin-3 - an emerging prognostic indicator in advanced head and neck carcinoma.

Galectin-3, is a multifunctional effector. It is the only chimera-type member of the galectin family of endogenous lectins, which share specificity with beta-galactosides and have a jelly-roll-like folding pattern. It's activity profile includes modulation of cell-cell and cell-extracellular matrix interactions and the regulation of proliferation and apoptosis/anoikis. While lectin histochemistry with plant/invertebrate proteins is routine practice and immunohistochemical analysis of endogenous lectins has been thoroughly examined, the application of an endogenous lectin as a marker is presently primarily a promising concept. The aims of our study were to test galectin-3 as a technical probe and to correlate staining by the tissue lectin, localising accessible ligands in situ, to clinicopathological characteristics and the prognosis of patients (relapse-free and overall survival) in advanced head and neck squamous cell cancer. We measured galectin-3-dependent staining in 53 surgically resected oropharyngeal and laryngeal cancer specimens (stage III or IV). Patients were divided into two groups based on a threshold of 5% positivity in the tumour cell population. The patient's degree of positivity was significantly correlated with their level of differentiation and keratinisation and lack of lymph node involvement (P=0.0001, P=0.0007 and P=0.0224, respectively). Periods of relapse-free and overall survival were significantly shortened when the tumour population failed to meet the positivity criterion, i.e. to harbour ligands for the endogenous lectin (P=0.0039 and P=0.0259, respectively). We conclude that (a) studies with an endogenous lectin as a marker are technically feasible and (b) detection of accessible galectin-3-specific ligands is an independent prognostic marker in advanced head and neck squamous cell cancer with therapeutic potential. Of note, histochemical application of an endogenous effector after its purification and labelling may bear relevance beyond the galectins.

Aged↗

PubMed2004

Thyroid surgery in children and adolescents.

Authors present 114 children and adolescents of the total 3865 patients that underwent surgery on the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University, Prague, Department of Otorhinolaryngology of IPVZ, Prague because of a thyroid disease in years 1991-2000. The male/female ratio in the group was 1:6.5, 16 (13.9%) males and 99 (86.1%) females. For non-malignant disease, the male/female ratio was 1:6.5 and for malignant disease, it was 1:5.4. Thyroid surgery was indicated for non-malignant disease in 82 (71.9%) cases--11 males and 71 females. Most frequently it was indicated because of Graves-Basedow and Hashimoto toxicosis--in 39 children (34.2%), in 5 children (4.4%) for toxic adenoma. Because of the polynodular goiter surgery was indicated in 13 cases (11.4%), in 22 cases (19.3%) for mononodular goiter. Three girls (2.6%) were recommended for surgery because of Hashimoto thyreoiditis and for mechanic syndrome in diffuse goiter one girl (0.9%). Malignant tumor was found in 32 children (28.1%)--5 males and 27 females. Most frequent histological type was papillary cancer--in 25 cases (21.9%). Follicular cancer was diagnosed in four cases (3.5%) and medullar cancer in three cases (2.6%). TNM classification in children and adults is summarized in Table 1. Surgery was carried out in two children with distant metastases (lung localization). In both children the pre-disease stage lasted more than 12 months. The first manifestation of the disease was a finding of enlarged and palpable nodes on the neck. The authors summarize indications for surgery of thyroid diseases in children and adolescents. A treatment of the thyroid gland is a teamwork. Indication for surgery is carried out by a pediatric endocrinologist in cooperation with a surgeon specialized in thyroid surgery. The possible identification of the recurrent laryngeal nerve by a surgery microscope is an unquestionable advance. Children and adults should be centralized into health-care centers capable not only of surgery, but also of endocrinology care. In children with a malignant disease there is a need for cooperation with a pediatric oncologist and a following oncological treatment on a nuclear medicine department. The authors summarize the information about today's thyroid surgery care possibilities for children and adolescents. They point out the differences in indications and the decision about extent of surgery in children and adolescents.

Adenocarcinoma↗

PubMed2004

Major surgery in elderly head and neck cancer patients: immediate and long-term surgical results and complication rates.

BACKGROUND: Evaluation of immediate and long-term surgical results in major surgery for the head and neck tumours in elderly patients and identification of tumour and patient related factors that affect the incidence and severity of surgical and medical complications. METHODS: Retrospective analysis of a series of 24 consecutive patients aged 70 and over with head and neck tumours undergoing extensive surgical resections with reconstruction with/without osseous and/or soft tissue transfer. Patients' demographics and surgery and tumour related data were extracted from appropriate charts and recorded. Pre-existent comorbid conditions, immediate and long-term surgical and medical complications were analysed. Pre-existing comorbidities were graded and staged using the Comorbidity Data Collection Form. Postoperative surgical and medical complications were scored according to their severity. RESULTS: Overall complication rate in present study was 63% and 54% of patients experienced clinically important surgical and/or medical complications. However, medium admission time remained at 16 days. Presence of advanced comorbidity, longer operative times and advanced stage of disease seemed to influence the development of surgical or medical complications. CONCLUSIONS: Major surgery for head and neck tumours is of great value even in elderly patients providing very good surgical results with acceptable complication rates. The choice of treatment modality should be based on all factors affecting the treatment outcomes. In particular, the presence of the co-existent underlying diseases should be assessed meticulously and in cases with clinically important comorbidities the surgical treatment stress should be reduced to minimum.

Adenocarcinoma↗

PubMed2004

Comparative analysis of alpha2,3/2,6-linked N-acetylneuraminic acid and cytokeratin expression in head and neck squamous cell carcinoma.

Head and neck squamous cell cancer (HNSCC) requires precise characterization of their biological properties to better stratify treatment approaches. Some biological features of tumor cells are related to altered glycosylation of their surface. This study characterized alpha2,3/6-N-acetylneuraminic acid (NeuNAc) expression in adult squamous epithelia of primary and metastatic HNSCC in relation to expression of well established differentiation markers, such as cytokeratins. The expression of NeuNAc was assessed by plant lectins: Maackia amurensis agglutinin type 2 (MAA) and Sambucus nigra agglutinin (SNA) specific for alpha2,3NeuNAc and alpha2,6NeuNAc, respectively. Double labeling studies at the single-cell level were performed to compare alpha2,3/6NeuNAc linkage with expression of intermediate filaments. In studied normal adult epithelia, predominantly basal expression of alpha2,6NeuNAc and suprabasal expression of alpha2,3NeuNAc was seen, showing their differentiation-dependent linkage. The cells with markers of terminal differentiation (i.e. CK10+ alpha2,3NeuNAc+ alpha2,6NeuNAc-) prevailed in HNSCC, with increasing proportion from differentiation grade G1 to G3. High proportions of cytokeratin pCK37+ carcinoma cells occurred in all studied tumors and were accompanied by a hypersialylated phenotype (i.e. alpha2,3 NeuNAc+ alpha2,6NeuNAc+) not generally seen in non-transformed epithelia. It is hypothesized that these cells could be the pool for tumor spreading in the organism. Monitoring HNSCC using multiparameter phenotype analysis can produce new data important for the understanding of the biological behavior of HNSCC, and useful for the treatment rationalization.

Biotinylation↗

PubMed2004

Serum levels of growth factors HGF (Hepatocyte Growth Factor), TGFbeta1 (transforming growth factor beta1) and IGF-I (Insulin Like Growth Factor I) in parathyroid tumors.

INTRODUCTION: HGF (Hepatocyte Growth Factor), TGFbeta1 (Transforming Growth Factor beta1) and IGF-I (Insulin Like Growth Factor I) are cytokines that are involved in the parathyroid tumors formation and growth. We tried to determine, if there are changes and relationships in the production of these cytokines by tumor cells of parathyroid tumors. MATERIAL AND METHODS: We determined concentrations of HGF, TGFbeta1 and IGF-I in serum from peripheral blood of 16 patients with parathyroid adenoma and of 8 patients with parathyroid secondary hyperplasia before and after parathyroidectomy. Results were compared with serum levels in healthy people. RESULTS: Both preoperative and postoperative HGF serum levels in patients with parathyroid adenoma and secondary hyperplasia are significantly higher than in healthy people. Preoperative and postoperative serum levels of TGFbeta1 in parathyroid adenoma and postoperative TGFb1 serum levels in parathyroid secondary hyperplasia are higher, compared with those in the healthy population and in parathyroid secondary hyperplasia preoperatively. There are no significant differences of IGF-I serum levels among the all investigated groups of patients. CONCLUSIONS: Changes in the growth factors production by parathyroid tumor cells are reflected by their concentrations in peripheral blood. The elevation of HGF serum levels in patients with parathyroid adenoma and hyperplasia can be explained by very high HGF production by tumor cells. Nevertheless, there is no decrease of HGF serum levels after the parathyroidectomy. That may be the result of the extratumoral production of this cytokine. Also TGFbeta1 and IGF-I serum levels indicate high possibility of the extratumoral production of these cytokines. Higher postoperative IGF-I serum levels (but not significantly) in parathyroid secondary hyperplasia are in accordance with its bone production.

Adenoma↗

PubMed2003

Thyroid abscess at an adolescent age.

We report a case of thyroid abscess in a 17-year-old girl. She was presented with swelling and pain in the region of the left thyroid lobe. The diagnosis was confirmed by ultrasonography and fine needle aspiration. After incision, evacuation of the pus and antibiotic treatment manifestations of disease disappeared. Barium swallow did not prove any hypopharyngeal fistula. The girl is now without any problems for 3 years. The patient had infectious mononucleosis 2 months prior development of the thyroid abscess. We contemplate that it may had changed the immunological state that facilitated this rare inflammation.

Abscess↗

PubMed2003

Galectin-3, an endogenous lectin, as a tool for monitoring cell differentiation in head and neck carcinomas with implications for lectin-glycan functionality.

OBJECTIVE: Galectin-3 is an endogenous lectin that reacts with glycan epitopes of membrane and extracellular glycoproteins, including integrins, fibronectin, laminin and tetraspanins. Its expression, and also the presentation of its glycoligands, is controlled in a differentiation-dependent manner in squamous epithelia. The aim of this study was to monitor the carbohydrate-dependent binding of labeled galectin-3 to primary head and neck squamous cell carcinomas (from the tonsil, base of the tongue and larynx) and lymph node metastases. MATERIAL AND METHODS: Double labeling (using antibodies against desmoplakin-1, Ki-67 and cytokeratins) at the single-cell level was employed to cytologically characterize cells reacting with galectin-3. RESULTS: Galectin-3 binds a non-proliferating pool of tumor cells. Colocalization of galectin-3 binding sites with desmosomal proteins may indicate a role for this endogenous lectin in the formation of intercellular contacts of the desmosomal type. Cytokeratin-10-positive tumor cells also presented galectin-3-reactive binding sites on the surface; however, cytokeratin-10-free cells were also recognized by this lectin. CONCLUSION: These findings intimate that galectin-3 may represent a new tool for monitoring the degree of cell differentiation in carcinomas originating from the transformation of squamous cell epithelia.

Biomarkers, Tumor↗

PubMed2003

Serum levels of angiogenic growth factors in patients with thyroid gland tumors and parathyroid adenoma.

OBJECTIVE: Angiogenic growth factors bFGF and VEGF ensure vascularisation of the growing tumor tissue. We decided to investigate their peripheral serum concentrations in patients with thyroid gland adenoma and papillary carcinoma and with parathyroid adenoma. We wanted to find the possible serum marker of these tumor diseases. METHODS: 28 patients with thyroid gland tumor (14x adenoma, 14x papillary carcinoma) and 12 patients with parathyroid gland adenoma. Growth factors serum levels were measured by ELISA method. RESULTS: We found significantly higher serum levels of bFGF in both groups of patients with thyroid adenoma (4.93 +/- 3.42 ng/ml) and papillary carcinoma (5.69 +/- 5.58 ng/ml) compared to the healthy population (1.47 +/- 1.77 ng/ml). There were no significant differences of VEGF serum levels between all examined groups of patients (adenoma 213 +/- 197, papillary carcinoma 210 +/- 179, healthy 227 +/- 231 pg/ml). We found significantly higher serum levels of bFGF in patients with parathyroid gland adenoma (7.59 +/- 9.12 ng/ml) compared to those in healthy people (1.47 +/- 1.77 ng/ml). CONCLUSIONS: Higher bFGF serum concentrations in patients with thyroid and parathyroid tumors are in accordance with their immunohistochemical tissue levels described in the literature. Not so in VEGF. bFGF may be a serum marker of thyroid and parathyroid neoplasms.

Adenoma↗

PubMed2002

The role of dendritic cells in the pharynx.

The tonsils are organized as lymphoepithelial structures that play an important role in protecting both the upper respiratory and alimentary tract regions against incoming antigens. This function requires dendritic cells, professional antigen-presenting cells that act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material. This article gives a brief review on dendritic cells with regard to their origin, life cycle and functions in the pharyngeal mucosa. The regulation of immune responses in tonsils by dendritic cells is discussed. Their importance in some disease states is also mentioned.

Cell Cycle↗

PubMed2002

Analysis of binding of mannosides in relation to Langerin (CD207) in Langerhans cells of normal and transformed epithelia.

Tandem-repeat C-type lectins (pattern-recognition receptors) with specificity for mannosides are intimately involved in antigen recognition, uptake, routing and presentation in macrophages and dendritic cells. In Langerhans cells, Langerin (CD207), a type-II transmembrane protein with a single C-type carbohydrate recognition domain attached to a heptad repeat in the neck region, which is likely to establish oligomers with an alpha-coiled-coil stalk, has been implicated in endocytosis and the formation of Birbeck granules. The structure of Langerin harbours essential motifs for Ca2+-binding and sugar accommodation. Lectin activity has previously been inferred by diminished antibody binding to cells in the presence of the glycan ligand mannan. In view of the complexity of the C-type lectin/lectin-like network, it is unclear what role Langerin plays for Langerhans cells in binding mannosides. In order to reveal in frozen tissue sections to what extent mannose-binding activity co-localizes with Langerin, we have used a synthetic marker, i.e. a neoglycoprotein carrying mannose maxiclusters, as a histochemical ligand, and computer-assisted fluorescence monitoring in a double-labelling procedure. Mannoside-binding capacity was detected in normal epithelial cells. Double labelling ensured the unambiguous assessment of the binding of the neoglycoprotein in Langerhans cells. Light-microscopically, its localization profile resembled the pattern of immunohistochemical detection of Langerin. This result has implications for suggesting rigorous controls in histochemical analysis of this cell type, because binding of kit reagents, i.e. mannose-rich glycoproteins horseradish peroxidase or avidin, to Langerin (or a spatially closely associated lectin) could yield false-positive signals. To show that recognition of carbohydrate ligands in dendritic cells is not restricted to mannose clusters, we have also documented binding of carrier-immobilized histo-blood group A trisaccharide, a ligand of galectin-3, which was not affected by the presence of a blocking antibody to Langerin. Remarkably, access to the carbohydrate recognition domain of Langerin appeared to be impaired in proliferatively active environments (malignancies, hair follicles), indicating presence of an endogenous ligand with high affinity to saturate the C-type lectin under these conditions.

Antigens, CD↗

PubMed2002

Defining the glycophenotype of squamous epithelia using plant and mammalian lectins. Differentiation-dependent expression of alpha2,6- and alpha2,3-linked N-acetylneuraminic acid in squamous epithelia and carcinomas, and its differential effect on binding of the endogenous lectins galectins-1 and -3.

A thorough characterization of the properties of squamous epithelial cells is necessary in order to improve our understanding of the functional aspects of normal development and malignant aberrations. Up to now, studies have focused almost exclusively on monitoring distinct protein markers. With our growing awareness of the coding function of glycan chains of cellular glycoconjugates and their interaction with receptors (lectins) in situ, defining the glycophenotype of these cells has become an important issue. Whereas the commonly applied plant lectins are tools used to map the presence and localization of biochemically defined saccharide epitopes, the introduction of endogenous (mammalian) lectins to this analysis enables us to take the step from monitoring the presence of glycan to understanding the functional implications by revealing ligand properties of the detected epitope for tissue lectin. Thus, in this study we investigated a distinct aspect of glycosylation using plant and mammalian lectins, i.e. the linkage type of sialylation. We first mapped the expression profile of the type of sialylation (alpha2,3- or alpha2,6-linked) by plant lectins. Based on the hypothesis that this factor regulates accessibility of ligands for endogenous lectins we introduced two labeled galectins to this study. Galectin-3 (but not galectin-1) binding was related to cell differentiation in normal adult and developing epithelia, cultured epidermal cells, and carcinomas derived from these epithelia. The presented data suggest that alpha2,6-linked N-acetyl-D-neuraminic acid moieties could serve to mask galectin-3-reactive glycoepitopes. As a consequence, monitoring of the linkage type of sialic acid in glycans by plant lectins therefore has implications for the extent of glycan reactivity with endogenous lectins, pointing to a potential function of changes in sialylation type beyond these cell and lectin systems.

Animals↗

PubMedDate not supplied

Management of benign stenoses of the large airways in the university hospital in Prague, Czech Republic, in 1998-2003.

BACKGROUND: Clinically significant benign stenoses of the large airways develop in about 1% of patients after intubation. The management of benign stenoses is not unified around the world, nor are there any accepted methods for their screening. OBJECTIVES: The purpose of this study is to describe and compare results of interventional bronchoscopy and surgical therapy of benign stenoses as well as to propose an algorithm for the management of this airways disorder. METHODS: Prospective study on 80 consecutive patients with benign stenoses of the large airways admitted to the Pulmonary Department of the University Hospital of Prague-Motol. RESULTS: Sixty-two patients developed stenoses after endotracheal intubation or tracheostomy, in 18 patients the stenosis was caused by other diseases or pathological situations. Thirty-eight patients were sent for surgical resection of the stenotic part of the airways. 2 surgically treated patients developed recurrence of the stenosis and had to be reoperated on. Narrowing of the trachea at the site of end-to-end anastomosis developed in 6 other patients and was cured by interventional bronchoscopy. The remaining 42 patients were treated by interventional bronchoscopy (Nd-YAG laser, electrocautery, stent) which was curative in 35 patients. Sixty-five patients were alive at the time of evaluation, 15 patients died. Five of them died between 3 and 14 (median 4) months after surgery from a disease other than airway stenosis. Ten nonresected patients also died, with 1 exception, due to a disease other than airway stenosis; the median survival was 9 months. CONCLUSIONS: We recommend to assess the patient for surgery after the initial diagnosis and therapeutic bronchoscopy with dilatation of the stenosis. If the patient is not a suitable candidate for resection, interventional bronchoscopy is an appropriate alternative for the management of benign stenoses of the large airways.

Adolescent↗

PubMedDate not supplied

Coincidence of thyroid tumor and thyroglossal duct remnants. Review of the literature and presentation of three cases.

AIMS AND BACKGROUND: The coincidence of benign or malignant thyroid tumors with thyroglossal duct remnant (TDR) cysts is rare. Although the precise etiology is still unclear, thyroid origin and spread from a primary site have been suggested and this obviously has important implications for the therapeutic approach. Three cases of thyroglossal duct carcinoma are presented and its management is discussed on the basis of the current rationale for treatment of thyroid cancer. The indication for surgery depends on positive findings in the thyroid gland (nodules, FNAB). The aim of this study was to review our experience in the management of papillary thyroid diseases associated with TDR. MATERIALS AND METHODS: The records of three patients with thyroid tumors associated with TDR treated at the Department of ENT and Head and Neck Surgery of the First Medical Faculty UK of Prague between January 1991 and January 2001 were analyzed. We searched for risk factors of thyroid carcinoma: history of ionizing radiation, history of thyroid diseases, age, tumor size, tumor spread and histopathological factors. RESULTS: We used a triple approach consisting of clinical and ultrasound examination and fine-needle aspiration biopsy for preoperative assessment. Our diagnostic and therapeutic procedures included TDR excision (Sistrunk or Schlange procedure) and total thyroidectomy. Although the therapeutic approach could be a matter of discussion, most patients agreed with our suggestion of relatively radical but non-mutilating treatment. Postoperative radiation or radioiodine ablation is considered in cases of TDR carcinoma or thyroid carcinoma associated with TDR. Oncological follow-up included clinical and ultrasound examination three times during the first year, twice in the second year, and once yearly thereafter. Tumor marker evaluation and/or scintigraphy were performed 6, 12 and/or 24 months following surgery.

Adult↗