Molecular characterization of Canis familiaris oral papillomavirus 1 identified in naturally infected dogs from Northeast Brazil.

BACKGROUND: Canine papillomavirus (CPV) has 20 described types associated with papillomas or squamous cell carcinoma (SCC). Knowledge about CPV diversity is scarce. Studies on papillomaviruses that infect other hosts show substantial diversity with some types and variants being associated with cancer. HYPOTHESIS/OBJECTIVES: The aim of this study was to assess the genetic variability of the capsid L1 gene of CPV identified in lesions of naturally infected dogs from Brazil. ANIMALS: Six dogs presenting with oral and cutaneous warts from different veterinary clinics in Sergipe state, Northeast Brazil. METHODS AND MATERIALS: Nine skin biopsy samples were collected for histopathological and molecular analyses. Bioinformatics tools were used for genotyping and diversity analysis. Mutations were characterized based on their impact on the L1 protein structure. RESULTS: Sequences of CPV1 were obtained from exophytic papillomas. These sequences had at least five different mutations showing that all sequences were putative CPV1 variants. One CPV1 sequence, obtained from an oral SCC, had a highly destabilizing substitution in the L1 protein which was likely to be associated with changes in protein function. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the small number of cases analysed and the partial analysis of L1 nucleotide and amino acid sequences, this study has demonstrated diversity in CPV samples from Northeast Brazil. A putative new CPV1 variant associated with oral SCC, with novel protein structure changing mutations, was identified which may be important for understanding papillomavirus pathogenesis.

Comparative transcriptomic analysis of bovine papillomatosis.

BACKGROUND: Bovine papillomavirus (BPV) belongs to the Papillomaviridae family and infects epithelial cells of bovines and closely related animals, causing hyperproliferative lesions known as warts or papillomas, which may regress or progress to form benign or malignant tumors. The virus enters the host cell and interacts with it by altering the regulation of genes that are responsible for controlling the cell cycle, thus triggering lesion formation. It is not yet known which host genes are regulated by viral infection. Therefore, the objective of this study was to make use of next-generation RNA sequencing methods to identify differentially expressed genes associated with BPV infection, which might elucidate possible marker genes that could be used to control the disease. RESULTS: Transcriptome analysis revealed that 1343 genes were differentially regulated (FDR < 0.05). A comparison of gene expression in infected and noninfected cows indicated that 655 genes were significantly upregulated, and 688 genes were significantly downregulated. Most differentially expressed genes were associated with BPV infection pathways, which supports the hypothesis that viral infection was the mechanism associated with this regulation. CONCLUSIONS: This is the first study that focused on a large-scale evaluation of gene expression associated with BPV infection, which is important to identify possible metabolic pathways regulated by host genes for lesion development. In addition, novel targets could be identified in order to find ligands that interact with BPV, with the aim of interrupting the infection cycle.

Potential clinical implications of HPV status and expressions of p53 and cyclin D1 among oropharyngeal cancer patients.

BACKGROUND: There is increasing evidence that high-risk human papillomavirus plays significant role in oropharyngeal cancer; however, there is lack of knowledge on the interplay between the virus and its downstream-related molecules and their possible prognostic values. The objectives of the study are to better understand the interplay of the HR-HPV and its associated downstream molecules and to evaluate potential biomarkers for patient outcomes. METHODS: We conducted a retrospective study with available formalin-fixed, paraffin-embedded tissue from 244 oropharyngeal cancer patients that received curative radiotherapy or concurrent chemoradiotherapy from 2000 to 2008. In addition to chart review, we performed HPV DNA and RNA in situ hybridization and immunohistochemistry for p53, the retinoblastoma protein, p16, and cyclin D1 analysis. Cox proportional hazard and Kaplan-Meier survival analysis were used to determine the prognostic markers for clinical outcomes. RESULTS: Patients averaged 57.3 ± 9.4 year-old and were mostly males (76.2%) and ever-smokers (76.2%). All patients received curative radiotherapy, and 44.3% received concurrent chemoradiotherapy. We detected the human papillomavirus in 77.9% of study patients. Ever-smokers, more advanced tumor stage, and receiving radiotherapy only had poorer 5-year overall survival, disease-specific survival, and loco-regional recurrence. Cases with positive human papillomavirus and p53 overexpression had poorer disease-specific survival. Cases without human papillomavirus, but cyclin D1 overexpression, were associated with poorer 5-year overall survival. CONCLUSIONS: Our data suggest that additional p53 and cyclin D1 testing may benefit oropharyngeal cancer patients with known human papillomavirus status.

Improvement of wound tissue repair by chitosan films containing (-)-borneol, a bicyclic monoterpene alcohol, in rats.

The aim of this study was to investigate the wound-healing activity of (-)-borneol (BOR) incorporated in chitosan film on healing protocol in rodents. To assess the BOR wound-healing potential, male Wistar rats were subjected to a full-thickness excisional wound. The animals were divided into three groups: dressed with chitosan-based film (QUIN); dressed with chitosan-based film containing 0·5% BOR (QUIBO05); or dressed with chitosan-based film containing 1% BOR (QUIBO1). Dressing the wound areas and histological analysis were performed on the 3rd, 7th, 14th, and 21st days. The myeloperoxidase (MPO) activity was assessed on the third and seventh days after surgical procedures. Wounds dressed with chitosan-based film containing BOR reduced significantly the MPO activity (P < 0·001), showed significantly larger wound retraction rates (7 days, P < 0·05), improved the granulation reaction, and also provided better collagenisation density and arrangement during wound healing. It is suggested that BOR modulates the wound-healing process and is a promising compound to be used in wound care. This product may be quite useful in improving wound healing and could be a new biotechnological product with healing properties and clinical application. Further ongoing studies will enable us to understand the precise mechanisms whereby BOR improves the wound-healing process.

Osteossarcoma de mandíbula inicialmente mimetizando lesão do periápice dental: relato de caso / Osteosarcoma of mandible initially resembling lesion of dental periapex: a case report

O osteossarcoma é um tumor mesenquimal maligno, no qual as células cancerosas produzem matriz óssea. É o tumor maligno primário mais comum do osso, responsável por aproximadamente 20 por cento dos sarcomas, sendo que 5 por cento destes ocorrem nos maxilares. Possuem variados aspectos não só clínicos e histopatológicos como também no curso e prognóstico. Este artigo apresenta um relato de caso de paciente do sexo feminino, com 20 anos de idade, que nos foi encaminhada apresentando aumento de volume na região de pré-molar inferior esquerdo. Após diagnóstico clínico de lesão do periápice dental, a paciente foi submetida previamente a tratamento endodôntico do dente envolvido, a partir do qual, em um período de 11 dias, pode-se observar um considerável aumento da lesão provocando visível assimetria facial. A radiografia oclusal mostrava imagem compatível com área de destruicão óssea e formacão de osso anormal na região, com cortical externa exibindo evidente radiopacidade semelhante a raios de sol, sugerindo o diagnóstico de osteossarcoma. A lesão foi biopsiada e obteve-se o diagnóstico histopatológico de osteossarcoma. A paciente foi então submetida à mandibulectomia parcial e uma reconstrucão da área, usando osso de costela e enxerto de pele da nádega, para o revestimento da mucosa oral envolvida. Aos 8 meses após a cirurgia houve recorrência local da lesão e a paciente foi a óbito aproximadamente 1 ano depois da recidiva.

Osteosarcoma of mandible initially resembling lesion of dental periapex: a case report.

Osteosarcoma is a malignant mesenchymal tumor whose cancerous cells produce osteoid matrix. It is the most common primary malignant bone tumor, accounting for approximately 20% of the sarcomas, but only 5% of the osteosarcomas occur in the jaws. They present various clinical and histological aspects, as well as variable disease progression and outcome. This article shows a case report of a 20-year-old woman who presented swelling near the mandibular left premolar. After clinical diagnosis of lesion of the dental periapex, the patient initially underwent endodontic treatment of the tooth involved. Thereafter, in a period of eleven days, a significant increase of the lesion could be observed, resulting in visible facial asymmetry. The occlusal radiographic view showed an area of bone destruction and abnormal bone formation in the region. The external cortical portion showed clear radiopacity resembling sunrays, suggesting the diagnosis of osteosarcoma. The treatment comprised partial mandibulectomy and reconstruction of the area, using bone of the rib and skin graft from the buttock for the oral mucosa involved. Eight months after surgery, there was local recurrence of the lesion and the patient died approximately one year after relapse.

HPV e carcinogênese oral: revisäo bibliográfica / HPV and oral carcinogenesis: a bibliographic review

O Papilomavírus humano (HPV) é um vírus ubíquo de DNA, epiteliotrópico, que tem a pele e as mucosas como principais sítios de infecçäo. Ultimamente, a sua associaçäo com neoplasias benignas e malignas da cavidade oral, principalmente o carcinoma epidermóide, tem sido mais evidente. O seu achado comum em epitélio de mucosa oral normal, amplamente divulgado na literatura, näo permite inferências mais precisas quanto ao seu papel na carcinogênese (se agente etiológico principal, coadjuvante ou simples habitante do epitélio de revestimento da mucosa oral). Säo mais de 100 tipos já identificados, dos quais 24 já foram localizados na cavidade oral. Desses, 4 säo particularmente importantes, os tipos 6 e 11 (que estäo envolvidos nas lesöes benignas do epitélio oral) e 16 e 18 (comprovadamente carcinogênicos e possivelmente envolvidos na etiologia de determinados carcinomas epidermóides orais). A açäo desses dois últimos tipos está principalmente associada às oncoproteínas E6 e E7 produzidas pelos mesmos. A E6 liga-se, seqüestra e degrada a p53, importante proteína supressora de tumor. A segunda liga-se e seqüestra a pRb, também supressora de tumor, facilitando a liberaçäo de E2F. Apesar do aprimoramento das técnicas de detecçäo do HPV nas lesöes de mucosa oral, o seu envolvimento direto com os carcinomas orais näo foi ainda devidamente comprovado, todavia a sua açäo sinérgica com outros carcinógenos químicos e físicos, tais como o fumo e o álcool, em determinados carcinomas epidermóides nos parece o caminho mais correto para explicar a açäo do papilomavírus humano na carcinogênese oral