Changes of procollagen type III N-terminal propeptide (PIIINP) concentrations during healing of mandible fractures treated with biodegradable and titanium fixations.

PURPOSE: The aims of the study were to evaluate procollagen type III N-terminal propeptide (PIIINP) concentrations in blood serum of males in the course of normal healing of mandible fractures, and to determine the correlations between kinetic changes of PIIINP, stages of fracture healing and the applied treatment. MATERIAL AND METHODS: We collected blood serum samples from 43 male patients aged between 20 and 30 years, treated for mandible fractures. The patients were divided into 2 groups depending on the type of osteosynthesis used for immobilization of the fragments. Group I (n=10) consisted of patients whose reduced bone fragments were fixed with biodegradable fixations, while group II (n=33) included patients with titanium osteosynthesis devices. The control group (n=25) consisted of healthy males at the same age. PIIINP concentrations were determined with the radioimmunological method (RIA). RESULTS: We found a significant increase in PIIINP concentrations in both study groups (I and II) at defined stages of mandible fracture healing. Differences were noticed in the dynamics of the increase depending on the type of applied osteosynthesis devices. CONCLUSION: The results point to the fact that the injury and/or mandible fracture increase the collagen type III metabolism and its dynamics depends on the type of the used bone fixation.

Overexpression of B cell-activating factor (BAFF) in neutrophils of oral cavity cancer patients - preliminary study.

In the present study the expression of tumor-promoting B cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily (TNF) in neutrophils from oral cavity cancer patients, was examined by real-time PCR. For the purpose of comparison, the expression of BAFF protein was assessed in autologous peripheral blood mononuclear cells (PBMCs). An important question of this study has also been to explain the role of NF-κB in the induction of BAFF molecule. The increased expression of BAFF at the mRNA and protein levels in neutrophils and mononuclear cells of patients before and after treatment were accompanied by the increased expression of phospho-IκB protein level. Demonstrated excessive expression and secretion of BAFF by examined leukocytes suggest a tumor-promoting activity of those cells in oral cavity cancer patients. The overexpression of BAFF, observed at mRNA and protein levels in PMNs and PBMCs, as well as the secretion of soluble form of sBAFF by these cells, accompany the increased concentrations of sBAFF in the serum of patients. Observations above suggest that the modulation of BAFF molecules in examined leukocytes and the levels thereof in the serum may have future implications for immunotherapy of oral cavity cancer patients.

IL-17 family cytokines in neutrophils of patients with oral epithelial squamous cell carcinoma.

UNLABELLED: Epithelial squamous cell carcinoma is the predominant histological type among cancers of the head and neck. It is characterised by high growth dynamics and a low survival rate of patients. The usefulness of various markers and prognostic factors is assessed to improve treatment results in patients with epithelial squamous cell carcinoma.

The involvement of neutrophils (PMNs) in the neoplastic process and scarce evidence for the role of interleukin 17 (IL-17) family cytokines in these reactions encouraged us to undertake a study in this field. We assessed the expression and capability of neutrophils in patients with oral epithelial squamous cell carcinoma to release IL-17E and IL-17A in relation to their serum levels and expression of the specific receptors, i.e. IL-17R and IL-17BR. For the sake of comparison, the expressions of the proteins examined were assessed in autologous peripheral blood mononuclear cells (PBMCs). The levels were determined in the patients prior to treatment, taking into consideration the stage of the disease according to TNM classification.

Western blot analysis revealed no differences in the expressions of IL-17E and IL-17A either in PMNs or PBMCs of the patients as compared to the healthy subjects. However, the expressions of IL-17BR and IL-17R were found to be higher in both groups of cells in cancer patients as compared to the control. The use of ELISA method revealed that the levels of IL-17E and IL-17A were higher in cell supernatants and blood serum of the patients than of the healthy subjects. No differences were noted in the protein expression in the cells or concentration in supernatants of the patients with different stages of the disease.

Our findings as well as observations reported by other authors seem to indicate some new aspects of the biological role of IL-17 family cytokines, not only as markers of the inflammatory process but also as indicators of leukocyte activity in IL-17A and IL-17E-dependent reactions in patients with oral epithelial squamous cell carcinoma.

[Radiation induced leiomyosarcoma. Review of literature and case report]. / Miesniak miesakowy gladkokomórkowy indukowany radioterapia. Przeglad literatury i opis przypadku.

Post-irradiation sarcomas of head and neck appear seldom, and among them leiomyosarcoma (LMS) is exceptionally rare. 11 cases of this tumour, associated with previous irradiation and situated in this anatomical area have been described so far. The aim of this study was to describe 56 year-old patient with LMS and to compare this case with the others described in the literature. What brought our attention were scanty clinical symptoms coexisted with extensive radiological changes. Radiotherapy can give rise to the development of LMS in different moments of time after the treatment of primary tumor has been finished. In this aspect patients who undergone radiotherapy in the early stage of live and who are more susceptible to this kind of treatment should be followed up more closely and carefully.

Tryptophan and its metabolites in patients with oral squamous cell carcinoma: preliminary study.

PURPOSE: It has been showed that tryptophan (TRP) degradation has been linked to modulation of cancer cell proliferation. The aim of our study was to estimate the concentration of TRP and its derivatives, such as anthranilic (AA) and kynurenic acid (KYNA) in plasma, saliva, squamous cell carcinoma (SCC) tissues and healthy oral mucosa in patients with oral SCC. MATERIAL AND METHODS: The study was performed on plasma, non-stimulated, mixed saliva and squamous cell carcinoma tissues and healthy oral mucosa in patients with oral SCC. The concentration of TRP and its metabolites were determined by high-performance liquid chromatography (HPLC). RESULTS: In plasma the concentration of TRP was 33.73 +/- 2.52 microM, of KYNA was 26.97 +/- 5.35 nM and of AA was 32.40 +/- 2.30 nM. In saliva the concentration of TRP was 3.81 +/- 0.62 microM, of KYNA was 8.06 +/- 1.86 nM and of AA was 20.41 +/- 10.77 nM. In cancer tissues the levels of TRP (30.21 +/- 5.88 microM), KYNA (15.85 +/- 1 .82 nM) and AA (265.32 +/- 1 51.45 nM) were higher in respect to the concentration of TRP (13.28 +/- 0.62 microM), KYNA (12.75 +/- 2.28 nM) and AA (31.68 +/- 8.89 nM) in normal tissues. The increase in the content of TRP, KYNA and AA in cancer tissues reached 127.48 +/- 5.95%, 24.31 +/- 4.35% and 737.50 +/- 206.96%, respectively. CONCLUSIONS: Our study has demonstrated the change of TPR metabolism, which is reflected by the increase TRP, AA and KYNA concentrations in patients with oral squamous cell carcinoma. We can suppose that these substances may be one of many factors responsible for cancer development.

Evaluation of secretory mucin concentration of patients with squamous cell carcinoma oral cavity.

PURPOSE: Secretory salivary mucins constitute a heterogenous group of glycoproteins, synthesized and secreted by submandibular, sublingual gland and small glands of oral mucosa. The most significant functions of mucins in case of oral cavity carcinoma are: participation in oral pellicle formation, lubrication and creation of heterotypic complexing. The aim of this study was to assess mucins concentration, and finally to establish the correlation between concentration of mucins in saliva and clinical advancement according to TNM. MATERIAL AND METHODS: The research was conducted on mixed resting and stimulated saliva of patients with oral squamous cell carcinoma. Mucin's concentration was measured one day before, and thirty days after surgical procedure. The volume of saliva was volumetrically determined, quantitative evaluation of mucins was accomplished by PAS method. RESULTS: In comparison with K group, a significant decrease of mucins was found in resting and stimulated saliva of patients with carcinoma in all degrees of clinical advancement. Mean value of mucin in resting and stimulated saliva after surgical treatment were lowered. The degree of carcinoma clinical advancement correlated negatively with mucin concentration. CONCLUSIONS: The decrease of mucin contained in saliva may be important in further evolution or progression of carcinoma. The results also suggest that saliva may be a significant diagnostic material in carcinoma research.

Salivary epidermal growth factor in oral cavity cancer.

Salivary epidermal growth factor (EGF) effect on oral cancer biology is unknown. We examined changes in minute volumes of whole resting and stimulated saliva, EGF concentration and its output (ELISA) in whole resting and stimulated saliva before and 2 weeks after surgical treatment in oral carcinoma patients compared to the control group. After stimulation salivary flow increased both in the control (P=0.003) and in the patients group--before (P=0.007) and after surgery (P=0.005). Higher stimulated saliva volume levels were observed before surgery than in post-treatment patients (P=0.032). A trend was seen with increasing EGF salivary concentrations after tumour excision both in resting (P=0.508) and stimulated (P=0.647) saliva. A similar ascending tendency of EGF output in stimulated saliva of post-treatment patients was observed (P=0.878). Decreased levels of EGF concentration in saliva before and its contrary tendency after surgical treatment may suggest an important role of EGF in oral cancer tumourogenesis.

Collagen type I and III metabolism in assessment of mandible fractures healing.

PURPOSE: The aim of this work was estimation of the PIIINP, PICP and ICTP concentrations in blood serum during non-complicated mandible fracture healing; settlement of dependences between kinetics of changes of examined markers with reference to particular bone fracture phases and applied treatment methods; the determination of usefulness of collagen metabolism markers type III and I for the monitoring of mandibular fracture healing. MATERIAL AND METHODS: The material was blood serum of men aged 20-30 years, who were treated for mandible fractures in Maxillofacial Clinic Medical University of Bialystok. Depending on the treating method, examined patients were divided into two groups. Patients treated with non-operative method were I group (n = 31), II group was made of patients treated with surgery (n = 33). The concentrations of markers measured on the 2nd, 14th, 42nd, 90th day after trauma and in II group these substances were measured additionally on the 2nd and 14th day after surgery. Control group consisted of 20 healthy men the same age. Concentrations of markers were measured with the radioimmunological method (RIA). RESULTS: Regular process of mandible fracture healing in men in various periods occurs with PICP, PIIINP and ICTP concentration changes in blood serum. CONCLUSIONS: Changes of maker concentration show that, mandible fracture healing treated non-operatively is a more dynamic process than stable osteosynthesis method applied. Lack of positive correlation of the PIIINP and PICP concentration in blood serum of patients in two examined groups can indicate on the different mechanisms of mandible fracture healing connected with different methods of the treatment.

TNFRs and IL-6R transmembrane receptors expression and release of their soluble forms by neutrophils and mononuclear cells from cancer patients.

TNF-alpha and IL-6 are multipotential mediators involved in the control of many host's reactions to tumour. Their biological effects are mediated through the membrane-bound receptors (TNFRp55, TNFRp75 and IL-16R respectively) which can exist in soluble forms. In the present study we compared release of soluble sTNFRp55, sTNFRp75 and sIL-6R with expression of their membrane-bound on PMN and PBMC. Cells were isolated from patients with cancer diseases with a different location and histological classification. We have found that alterations of membrane-bound TNFRp75 expression and in the secretion of soluble TNFRp75 form, as opposed to other receptors examined, are characteristic features of neutrophils and mononuclear cells isolated from cancer patients. The similar changes observed in the expression of TNFRp75 by PMN and PBMC appear to confirm a significant role of PMN in the tumour response mediated by TNF-alpha. Furthermore, the altered membrane-bound TNFRp75 expression and sTNFRp75 secretion appear to depend on the tumour type.

The concentration of C-terminal propeptide of type I procollagen in blood serum in the course of mandibular fracture healing (preliminary report).

One of the basic measures of quality of repairing processes of soft tissue and bone injury is collagen synthesis. C-terminal propeptide of type I procollagen (PICP) is admitted index of type I collagen biosynthesis. The aim of the study was estimation of PICP concentrations in the course of fracture repair process in relation to the treatment method. The material of investigations was blood serum of 25 men (age 20-30 years) with fracture of mandible. The patients were divided into 2 groups depending on the method of treatment: I group was patients treated non-surgical method (n = 12); II group--surgical method (n = 13). Blood samples in the first group were taken on 2nd, 14th, 42nd, 90th day of healing process and additionally on 2nd and 14th day after surgery--in the second group. The PICP concentrations in blood serum were determined by RIA method. Statistical analysis of results shown significant increase of PICP concentrations in I group of patients in 14th (167.1 +/- 42.8 micrograms/L) and in 42nd (216.0 +/- 59.1 micrograms/L) day of healing process in comparison to the values in the second day after injury--the first study (124.3 +/- 41.8 micrograms/L). In the II group of patients the statistically significant increase of PICP concentration in 14th day after surgical procedure (156.9 +/- 30.5 micrograms/L), 42nd (163.1 +/- 35.3 micrograms/L) and in 90th (153.1 +/- 40.2 micrograms/L) day of healing process after injury in comparison to the values in the second day after injury--the first study (119.9 +/- 35.8 micrograms/L). The results indicate, that a normal course of mandibular fracture healing influences the change in PICP concentrations in serum in examined men. A different dynamics of PICP concentrations, observed in the serum in patients with mandibular fractures treated surgically and non-surgically, suggests various mechanisms of bone tissue reconstruction connected with the method of treatment.

Insulin-like growth factor-I (IGF-I) in serum and bone tissue during rat mandible fracture healing.

Insulin-like growth factor-I (IGF-I) is potent stimulator of proliferation and differentiation of osteoblasts, the biosynthesis of collagen type-I and noncollagenous proteins and alkaline phosphatase activity. The role of IGF-I in bone repair has not as yet been clearly defined. The aim of the present study was the quantitative analysis of IGF-I in the serum and tissue in four phases of fractured jaws healing in rat models. IGF-I concentrations in the serum and bone extracts were determined by RIA. In respect to the control group (K) the significant increase of IGF-I occurred in the serum in phase I (211 +/- 68 ng/ml, K-153 +/- 50 ng/ml) (p < 0.05). At the tissue levels a statistically significant increase in IGF-I was confirmed in phase II (262 +/- 60 ng/g, K-182 +/- 56 ng/g) (p < 0.05). The present results demonstrate that in rat models with fractured jaws in the first two phases of healing elevated levels of IGF-I in the serum and bone tissue were observed which indicate the significant role of this polypeptide in the early healing stages.

Influence of secretin and caerulein on acid phosphatase activity in human saliva.

Experimental studies have demonstrated a structural and functional correlation between the pancreas and salivary glands. Therefore, one may suppose that caerulein plus secretin, used in functional exploration of the exocrine pancreas, could exert an influence on acid phosphatase activity (AcP) and its isoenzymes (tartrate sensitive-TsAcP, tartrate resistant-TRAP acid phosphatases) in whole saliva in humans. The current study was conducted in 14 asymptomatic volunteers (six woman and eight men, mean age 34, range 27-45). Salivary secretions were collected under basal conditions (intravenous infusion of 0.15 mol l-1 NaCl) and during intravenous infusion of secretin plus caerulein at different doses. Stimulation with secretin (50 mKE kg-1 min-1) and caerulein (2.5 ng kg-1 min-1) resulted in a marked and rapid decrease of salivary flow rate. TRAP activity decreased during the first 20 min of hormonal infusion (1.09 +/- 0.19 mU ml-1 vs. 1.93 +/- 0.18 mU ml-1, 1.16 +/- 0.12 mU ml-1 vs. 1.86 +/- 0.17 mU ml-1, p < 0.05). AcP and TsAcP activity during intravenous infusion of secretin plus caerulein remained unchanged. These results point to a wider than expected participation of the digestive system in hormonal control of biochemical processes taking place inside the oral cavity.

Role of epidermal growth factor (EGF) in oesophageal mucosal integrity.

Oesophageal mucosa has well established protective mechanisms, which operate within pre-epithelial, epithelial and post-epithelial compartments. Since refluxed acid and pepsin always act from the luminal side of the mucosa, protective factors like EGF, operating as a part of pre-epithelial defence, are thought to be pivotal in the maintenance of the integrity of the oesophageal mucosa. The significant contribution of salivary EGF to the quality of the oesophageal mucosal barrier has been demonstrated in an experimental setting and in a clinical scenario. Patients with low salivary EGF levels are predisposed to severe oesophageal damage if they develop gastro-oesophageal reflux and are a high-risk group for development of Barrett's oesophagus. Not only the salivary glands but also the human oesophagus has a profound ability to elaborate and release EGF. Some changes in luminal release of EGF during oesophageal mucosal exposure to intraluminal damaging factors imply its role in the oesophageal protective mechanisms. To exert biological effects within the oesophageal mucosal compartment, EGF requires binding to the ligand-binding domain of its receptor. This process results in receptor dimerisation, autophosphorylation and activation of intracellular signal transduction pathways. EGF receptors are localised on the basolateral and luminal aspect of the mucosal cells playing an important role in fast regeneration of oesophageal epithelium through the high mitotic activity of its proliferative zone. An increase in the rate of salivary EGF secretion during masticatory stimulation suggests its potential therapeutic benefit in the treatment of patients with damaged oesophageal mucosa.