Evaluation of simulated bone lesion in the head of the mandible by using multislice computed tomography

Conventional radiography has shown limitation in acquiring image of the ATM region, thus, computed tomography (CT) scanning has been the best option to the present date for diagnosis, surgical planning and treatment of bone lesions, owing to its specific properties. OBJECTIVE: The aim of the study was to evaluate images of simulated bone lesions at the head of the mandible by multislice CT. MATERIAL AND METHODS: Spherical lesions were made with dental spherical drills (sizes 1, 3, and 6) and were evaluated by using multislice CT (64 rows), by two observers in two different occasions, deploying two protocols: axial, coronal, and sagittal images, and parasagittal images for pole visualization (anterior, lateral, posterior, medial and superior). Acquired images were then compared with those lesions in the dry mandible (gold standard) to evaluate the specificity and sensibility of both protocols. Statistical methods included: Kappa statistics, validity test and chi-square test. Results demonstrated the advantage of associating axial, coronal, and sagittal slices with parasagittal slices for lesion detection at the head of the mandible. RESULTS: There was no statistically significant difference between the types of protocols regarding a particular localization of lesions at the poles. CONCLUSIONS: Protocols for the assessment of the head of the mandible were established to improve the visualization of alterations of each of the poles of the mandible's head. The anterior and posterior poles were better visualized in lateral-medial planes while lateral, medial and superior poles were better visualized in the anterior-posterior plane.

Vimentin expression and the influence of Matrigel in cell lines of head and neck squamous cell carcinoma

Vimentin is a cytoeskeletal intermediate filament protein commonly observed in mesenchymal cells; however, it can also be found in malignant epithelial cells. It is demonstrated in several carcinomas, such as those of the cervix, breast and bladder, in which it is widely used as a marker of the epithelial to mesenchymal transition that takes place during embryogenesis and metastasis. Vimentin is associated with tumors that show a high degree of invasiveness, being detected in invasion front cells. Its expression seems to be influenced by the tumor microenvironment. The aim of this study was to evaluate vimentin expression in head and neck squamous cell carcinoma (HNSCC) cell lines, and to investigate the contribution of the microenvironment to its expression. HNSCC cell lines (HN6, HN30 and HN31) and an immortalized nontumorigenic cell line (HaCaT) were submitted to a three-dimensional assay with Matrigel. Cytoplasmatic staining of the HN6 cell line cultured without Matrigel and of the HN30 and HN31 cell lines cultured with Matrigel was demonstrated through immunohistochemistry. Western Blotting revealed a significant decrease in vimentin expression for the HN6 cell line and a significant increase for the HN30 and HN31 cell lines cultured with Matrigel. The results suggest that vimentin can be expressed in HNSCC cells and its presence is influenced by the microenvironment of a tumor.

Fine needle aspiration biopsy in the oral cavity and head and neck region

The objective of the current study was to evaluate the sensitivity, specificity and accuracy of fine needle aspiration biopsy (FNAB) of submucous nodules from the oral cavity and head and neck region as an auxiliary diagnostic tool. Fifty patients with nodule lesions in the oral cavity and the head and neck region were selected. All of them were submitted to FNAB and to either incisional or excisional biopsy. The diagnoses from the FNABs were compared with the biopsy diagnosis as the gold standard. All the cases of FNAB were analyzed by a single oral pathologist prior to the biopsy diagnosis. The results showed that the sensitivity of FNAB was 75%, its specificity was 96% and its accuracy was 58.8%. The false positive and false negative rates were 6.7% and 13.3%, respectively. The positive predictive value was 86% and the negative predictive value was 93%. The inconclusive rate was 16/50. FNAB displayed a high success rate for identifying both malignant and benign lesions, but a low accuracy for making a final diagnosis.

Acupuncture for the prevention of radiation-induced xerostomia in patients with head and neck cancer

The aim of this study was to evaluate the effectiveness of acupuncture in minimizing the severity of radiation-induced xerostomia in patients with head and neck cancer. A total of 24 consecutive patients receiving > 5000 cGy radiotherapy (RT) involving the major salivary glands bilaterally were assigned to either the preventive acupuncture group (PA, n = 12), treated with acupuncture before and during RT, or the control group (CT, n = 12), treated with RT and not receiving acupuncture. After RT completion, clinical response was assessed in all patients by syalometry, measuring the resting (RSFR) and stimulated (SSFR) salivary flow rates, and by the visual analogue scale (VAS) regarding dry mouth-related symptoms. Statistical analyses were performed with repeated-measures using a mixed-effect modeling procedure and analysis of variance. An alpha level of 0.05 was accepted for statistical significance. Although all patients exhibited some degree of impairment in salivary gland functioning after RT, significant differences were found between the groups. Patients in the PA group showed improved salivary flow rates (RSFR, SSFR; p < 0.001) and decreased xerostomia-related symptoms (VAS, p < 0.05) compared with patients in the CT group. Although PA treatment did not prevent the oral sequelae of RT completely, it significantly minimized the severity of radiation-induced xerostomia. The results suggest that acupuncture focused in a preventive approach can be a useful therapy in the management of patients with head and neck cancer undergoing RT.

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results

PURPOSE: Evaluate the bone tissue recovery following transplantation of ovine mesenchymal stem cells (MSC) from bone marrow and human immature dental-pulp stem cells (hIDPSC) in ovine model of induced osteonecrosis of femoral head (ONFH). METHODS: Eight sheep were divided in three experimental groups. First group was composed by four animals with ONFH induced by ethanol through central decompression (CD), for control group without any treatment. The second and third group were compose by two animals, six weeks after ONFH induction received transplantation of heterologous ovine MSC (CD + oMSC), and hIDPSC (CD + hIDPSC), respectively. In both experiments the cells were transplanted without application of any type of immunosupression protocol. RESULTS: Our data indicate that both cell types used in experiments were able to proliferate within injured site providing bone tissue recovery. The histological results obtained from CD+hIDPSC suggested that the bone regeneration in such animals was better than that observed in CD animals. CONCLUSION: Mesenchymal stem cell transplant in induced ovine osteonecrosis of femoral head by central decompression technique is safe, and apparently favors bone regeneration of damaged tissues.

Trichomycterus igobi, a new catfish species from the rio Iguaçu drainage: the largest head in Trichomycteridae (Siluriformes: Trichomycteridae)

A new species of Trichomycterus is described for the rio Iguaçu drainage in Southern Brazil. Trichomycterus igobi, new species, is readily distinguishable from all other species currently in the genus by its extremely large head (23.8-26.8 % SL), which is proportionally the largest head in any Trichomycteridae. That characteristic plus the relatively deep body result in a very short-bodied overall aspect, the most extremely such case in the genus Trichomycterus. Other diagnostic features that distinguish the new species from most or all of its congeners include a short caudal peduncle (15.4-19.7 % SL); an almost entirely cartilaginous second hypobranchial (with only vestigial ossification); a mesial expanded palatine ossification; a narrow cleithrum, falciform in shape; and the lack of a proximal posterior concavity on the third ceratobranchial. The new species seems to form a monophyletic group with T. stawiarski and other undescribed species (T. sp. C), also endemic to the rio Iguaçu. As putative synapomorphies, the three species share a rigid spine-like morphology of individual procurrent caudal-fin rays, an extended area of dorsal caudal-fin procurrent rays, and numerous branchiostegal rays (ten or eleven).

Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes. Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries. Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues. Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

LOCAL HEAD LOSS OF NON-COAXIAL EMITTERS INSERTED IN POLYETHYLENE PIPE

The design of a lateral line for drip irrigation requires accurate evaluation of head losses in not only the pipe but in the emitters as well. A procedure was developed to determine localized head losses within the emitters by the formulation of a mathematical model that accounts for the obstruction caused by the insertion point. These localized losses can be significant when compared with tire total head losses within the system due to the large number of emitters typically installed along the lateral line. Air experiment was carried out by altering flow characteristics to create Reynolds numbers (R) from 7,480 to 32,597 to provide turbulent flow and a maximum velocity of 2.0 m s(-1). The geometry of the emitter was determined by an optical projector and sensor An equation was formulated to facilitate the localized head loss calculation using the geometric characteristics of the emitter (emitter length, obstruction ratio, and contraction coefficient). The mathematical model was tested using laboratory measurements on four emitters. The local head loss was accurately estimated for the Uniram (difference of +13.6%) and Drip Net (difference of +7.7%) emitters, while appreciable deviations were found for the Twin Plus (-21.8%) and Tiran (+50%) emitters. The head loss estimated by the model was sensitive to the variations in the obstruction area of the emitter However, the variations in the local head loss did not result in significant variations in the maximum length of the lateral lines. In general, for all the analyzed emitters, a 50% increase in the local head loss for the emitters resulted in less than an 8% reduction in the maximum lateral length.

A reliable measure of similarity based on dependency for short time series: an application to gene expression networks

Background: Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges. Results: The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions. Conclusion: Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.

Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.

How much do smoking and alcohol consumption explain socioeconomic inequalities in head and neck cancer risk?

Background A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. Methods We conducted a case-control study in Sao Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. Results Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. Conclusions Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

Background: Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. Methods: Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results: The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions: The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.

Stratigraphy of near-valley head quaternary deposits and evidence of climate-driven slope-channel processes in southern Brazilian highlands

During the past 40 years colluvial and alluvial deposits have been used in Brazil as good indicators of regional landscape sensitivity to Quaternary environmental changes. In spite of the low resolution of most of the continental sedimentary record, geomorphology and sedimentology may favor palaeoenvironmental interpretation when supported by independent proxy data. This paper presents results obtained from pedostratigraphic sequences, in near-valley head sites of southern Brazilian highlands, based on geomorphologic. sedimentologic, micromorphologic, isotopic and palynologic data. Results point to environmental changes, with ages that coincide with Marine Isotopic Stages (MIS) 5b; 3; 2 and 1. During the late Pleistocene, although under temperatures and precipitation lower than today, the local record points to relatively wet local environments, where shallow soil-water saturated zones contributed to erosion and sedimentation during periods of climatic change, as during the transition between MIS 2 and MIS 1. Late Pleistocene events with ages that coincide with the Northern Hemisphere Younger Dryas are also depicted. During the mid Holocene, slope-wash deposits suggest a climate drier than today, probably under the influence of seasonally contrasted precipitation regimes. The predominance of overland flow-related sedimentary deposits suggests an excess of precipitation over evaporation that influenced local palaeohydrology. This environmental condition seems to be recurrent and explains how slope morphology had influenced pedogenesis and sedimentation in the study area. Due to relative sensitiveness, resilience and short source-to-sink sedimentary pathways, near-valley head sites deserve further attention in Quaternary studies in the humid tropics. (c) 2008 Elsevier B.A. All rights reserved.

Porphyrin-phospholipid interaction and ring metallation depending on the phospholipid polar head type

The interaction between a hydrophobically modified 5,10,15,20-tetrakis(4-N-tetradecyl-pyridyl) porphyrin and three phospholipids: two negatively charged, DMPA (the sodium salt of dimyristoyl-sn-glycero-phosphatidyl acid) and DMPG (the sodium salt of 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]) and a zwitterionic DMPC (dimyristoyl-sn-glycero-phosphatidylcholine), were studied by means of surface pressure isotherms and spectroscopic methods. The interaction results in partial or total metallation of the porphyrin with zinc ions in the presence of negatively charged phospholipids, as attested by UV-vis and luminescence spectroscopy of the transferred films. In the presence of the zwitterionic phospholipid no insertion of zinc ion in the porphyrin ring is detected. These results are relevant for the understanding of photosensitizer-lipid-carrier binding for use in photodynamic therapy. (C) 2010 Elsevier Inc. All rights reserved.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine`s potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mu g naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals. Cancer Gene Therapy (2009) 16, 598-608; doi:10.1038/cgt.2009.9; published online 6 February 2009