Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of β-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.
β-Tricalcium phosphate was combined with silica aerogel in composites prepared using the sol–gel technique and supercritical drying. The materials were used in this study to check their biological activity and bone regeneration potential with MG63 cell experiments. The composites were sintered in 100 °C steps in the range of 500–1000 °C. Their mechanical properties, porosities, and solubility were determined as a function of sintering temperature. Dissolution studies revealed that the released Ca-/P molar ratios appeared to be in the optimal range to support bone tissue induction. Cell viability, ALP activity, and type I collagen gene expression results all suggested that the sintering of the compound at approximately 700–800 °C as a scaffold could be more powerful in vivo to facilitate bone formation within a bone defect, compared to that documented previously by our research team. We did not observe any detrimental effect on cell viability. Both the alkaline phosphatase enzyme activity and the type I collagen gene expression were significantly higher compared with the control and the other aerogels heat-treated at different temperatures. The mesoporous silica-based aerogel composites containing β-tricalcium phosphate particles treated at temperatures lower than 1000 °C produced a positive effect on the osteoblastic activity of MG63 cells. An in vivo 6 month-long follow-up study of the mechanically strongest 1000 °C sample in rat calvaria experiments provided proof of a complete remodeling of the bone.
In this study, a mesoporous silica aerogel with beta-tricalcium phosphate (beta-TCP-AE) was manufactured. The effect of beta-TCP-AE on gene expressions (BMP2, BMP7, Runx2 and OSX) of SAOS-2 cells was tested. For the in vivo evaluation, the 'calvaria critical-size defect' model was used: following 1 and 3 months of the artificial surgical bone defects filled with beta-TCP-AE, histopathological analyses were performed. Gene expression studies demonstrated a mild osteoblastic differentiation of the SAOS-2 cells triggered after seven days of beta-TCP-AE treatment. Digital histology of rat's calvarial bone defects reconstructed with beta-TCP-AE showed that after 1 month, calcifications and early ossifications developed with the presence of capillary-rich fibrous inflammation and remnants of exogenous compounds which nearly disappeared by the third month, and replaced with multiple newly formed bone islets mediated by osteoblasts. Based on our results, this bioceramic compound appears to have favourable properties for the use as a scaffold in the reconstructive medical practice.
76 Aim The purpose of this study was to define the profile of patients with oral squamous cell carcinoma (OSCC) with an emphasis on an adult population in Northeastern Hungary. Methods Histopathological reports of 119 cases of OSCC treated at the Department of Pathology, University of Debrecen (Hungary) were retrospectively evaluated, and the data regarding age, gender, oral site affected, clinical and pathological features as well as risk factors were recorded and statistically analyzed for differences between patients younger and older than 45 years of age. Results Twenty-two patients (18.5%) were 45 years of age or below, the male:female ratio was 3.4:1. The floor of the mouth was the most frequent cancer site in the younger agegroup (50%), while lip (33%) was in the older group. The younger patients were diagnosed at an advanced stage (p=0.022), with more regional and distant metastases (p=0.028). The 5-year overall survival rate was lower, though not significantly, in the younger group (27.3% vs. 41.2%). Risk factors such as tobacco use and excessive alcohol consumption were present in 72.7% of the younger patients. Smoking habit significantly correlated with younger age (p=0.031). Conclusion OSCC is a serious oral health problem in Northeastern Hungary, as the rate of patients under the age of 45 years is extremely high. In this age group we found a decreasing overall survival time along with increasing intensity of risk habits. As the majority of the young patients presented with OSCC in advanced stages, early detection and treatment together with cessation of tobacco and alcohol abuse may improve patients’ survival.
Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV-associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high-grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real-time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10(2) copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10(5) vs. 7.8 × 10(5) copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High-risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.
Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions and mutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher’s exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls ( p < 0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 ( p = 0.043 and p = 0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.
We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) against 68 age-matched controls for the presence of Epstein-Barr virus (EBV). Apparently healthy mucosa was simultaneously sampled and examined in all patients. Paraffin-embedded tissue sections of all EBV-positive patients with OSCC were examined for latent membrane protein-1 (LMP-1) expression (demonstrable in most EBV-associated malignancies) using immunohistochemistry. The prevalence of EBV in the controls and in OSCC, OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%, 22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence of EBV in OSCC patients was significantly higher than in controls or in respective samples of the other two patient groups both in the lesion and in the healthy mucosa. Comparisons including only patients with EBV-negative lesions yielded similar results. Lesions of patients with OLP, but not of patients with OL, differed significantly from controls in EBV prevalence. In OSCC, LMP-1 expression was not detected, and EBV carriage was not significantly associated with any risk factors and did not influence the outcome. Although a high prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa of patients indicated that an aetiological role of EBV is unlikely.
In a previous pilot study, a significantly poorer outcome of laryngeal cancer was found in patients co‐infected with human papillomavirus (HPV) and genogroup 1 torque tenovirus (TTV). The present study aimed to collect data on the overall prevalence of TTVs on the prevalence of genogroup 1 TTV in two other malignancies associated with HPV, oral squamous cell cancer and cervical cancer, and in oral and cervical premalignant lesions (oral lichen planus, oral leukoplakia, cervical atypia). Oral samples from all patients were accompanied with a sample from the healthy mucosa. The overall prevalence of TTV was significantly higher both in oral squamous cell cancer and cervical cancer compared with other patient groups or with the respective controls. The prevalence of genogroup 1 TTV was significantly higher in lesions of oral squamous cell cancer and oral lichen planus, but not in lesions of oral leukoplakia (24.6%, 10.1%, and 4.5%, respectively), compared with the prevalence in the oral cavity of controls (1.4%). Co‐infection rates with genogroup 1 TTV and HPV were significantly higher in oral squamous cell cancer than in controls, oral lichen planus or oral leukoplakia patients (12.3%, 0.0%, 6.7%, and 4.5%, respectively). The prevalence of genogroup 1 TTV in all cervical samples were comparable. These data suggest that genogroup 1 TTV may be associated specifically with some head and neck mucosal disorders, but disproves a (co)carcinogenic role in oral cancer or cervical cancer as well as an association with HPV or with malignancies associated with HPV. J. Med. Virol. 81:1975–1981, 2009. © 2009 Wiley‐Liss, Inc.
In Hungary oral and pharyngeal cancers have been reported the fourth most common malignancy in males and the sixth for both sexes. The aim of the present study was to characterize oral squamous cell carcinoma (OSCC) patients in Northeastern Hungary. 119 randomly selected patients with OSCC were included in the study. Epidemiological data, clinicopathological parameters and the risk factors were registered. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients was diagnosed with early stage (I-II) lesions and moderately differentiated tumors. The 5-year overall survival rate was 38.7%. There was a significant correlation between survival and tumor size, lymph node involvement and clinical stage. At the time of diagnosis 65.5% of the patients were smokers. Smoking significantly correlated with younger age, male gender, advanced clinical stages and alcohol consumption. 75.5% of the patients consumed alcohol, 41.1% of them exceeding the conventional amount regularly. Drinking habit significantly correlated with younger age, male gender and tumor site i.e. gingiva, retromolar region, tongue. The dental status was acceptable only in 12.6% of the cases. There was a significant correlation between dental status and age, smoking and drinking habits. Clinical stage has the most significant impact on survival and the most important high-risk habits in Northeastern Hungary are smoking and alcohol consumption. Therefore, early detection and treatment, cessation of tobacco and alcohol abuse, and a regular dental care may improve patients' survival in the region.
The purpose of this study was to characterize the epidemiological data of oral squamous cell carcinoma (OSCC) patients in North-Eastern Hungary. The medical records of 119 randomly selected patients with OSCC admitted to the Department of Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were reviewed. Cases were identified according to the epidemiological data, as to site, tumor size, lymph node involvement, clinical stage, histological differentiation, treatment obtained, recurrence of disease and survival rate. There was an obvious male predominance (male:female = 5.2:1). The median age at diagnosis was 57.4 years. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients (58,8%) presented with early-stage (I-II) disease at the time of diagnosis, and 48.6% had moderately differentiated tumors. The most frequent therapeutic modality used was surgery with or with out of radiotherapy. Roughly one fifth of the cases (20.7%) experienced a recurrence of disease during the follow-up period. The overall 5-year survival rate was 38.7% (stage I: 68.3%, stage II: 31.0%, stage III: 22.6%, stage IV: 11.1%). There was a correlation between survival and tumor size, lymph node metastasis, clinical stage and surgical treatment (p < or = 0.05, respectively). We found no significant correlation between histological differentiation and survival. Clinical stage exerts the most strongly significant impact on survival. Therefore, early detection and proper surgical intervention enhance patients' survival most effectively.
The purpose of this study is to determine the possible etiological factors of oral squamous cell carcinoma (OSCC) in North-Eastern Hungary. The medical records of 119 randomly selected patients with OSCC admitted to the Department of Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were reviewed. The following risk factors were investigated: tobacco and alcohol consumption, dental status, rural vs. urban residence, and high risk HPV infection. The presence of HPV DNA has been evaluated by polymerase chain reaction from the tissue samples. Results were correlated with clinical data. At the time of diagnosis 65.5 percent of the patients were smokers. Under the age of 45 the rate was 86.4%. Smoking significantly correlated with younger age, male gender, advanced clinical stages and alcohol consumption. The majority of the patients (75.5%) consumed alcohol, 41.1% regularly over the acceptable range. Drinking habit significantly correlated with younger age, male gender and tumor site (gingiva, retromolar region, tongue). HR-HPV types were detected in 42.8% of samples tested. HPV DNA presence was not related to gender, clinical stage, histological grade or other risk factors. Authors found weak correlation between HR-HPV positivity, younger patient age and better 5-year survival rate. The dental status was acceptable only in 12.6 percent of the cases. There was a correlation between dental status and age, smoking and drinking habits. No significant urban-rural differences were found. In the study population the most important risk factor for developing oral cancer is tobacco smoking followed by alcohol consumption. Avoidance of tobacco smoking and a reduced amount of alcohol, together with healthy nutrition and regular dental care should be emphasized.