Combining gene therapy with other therapeutic strategies and imaging agents for cancer theranostics.

Cancer is one of the most prevalent and deadly diseases in the world, to which conventional treatment options, such as chemotherapy and radiotherapy, have been applied to overcome the disease or used in a palliative manner to enhance the quality of life of the patient. However, there is an urgent need to develop new preventive and treatment strategies to overcome the limitations of the commonly used approaches. The field of cancer nanomedicine, and more recently the field of nanotheranostics, where imaging and therapeutic agents are combined in a single platform, provide new opportunities for the treatment and the diagnosis of cancer. This combination could bring us closer to a more personalized and cared-for therapy, in opposition to the conventional and standardized approaches. Gene therapy is a promising strategy for the treatment of cancer that requires a transport system to efficiently deliver the genetic material into the target cells. Hence, the main purpose of this work was to review recent findings and developments regarding theranostic nanosystems that incorporate both gene therapy and imaging agents for cancer treatment.

Oral leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis: Analysis of 953 patients focusing on oral epithelial dysplasia.

BACKGROUND: To analyse the clinical and histological characteristics from a series of oral leukoplakias, leukoerythroplakias, erythroplakias and actinic cheilitis diagnosed in a 14-year period. METHODS: The files were reviewed and all cases diagnosed as leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis were selected. Clinical information was obtained from the biopsy submission forms, and histological review was performed in all cases. RESULTS: Final sample included 953 lesions, mostly affecting females (534, 56%), and 87.5% of the patients were 41 to 80 years old. The most commonly affected regions were the lower lip (20.1%), tongue (18.1%) and buccal mucosa (16.9%). Leukoplakias, actinic cheilitis, leukoerythroplakias and erythroplakias represented, respectively, 74.6%, 15.2%, 9.3% and 0.8% of the sample. Most cases presented no dysplasia (42.1%) or mild dysplasia (33.5%). Lesions in the tongue, floor of mouth and lower lip, as well as lesions that presented hyperparakeratosis, showed higher frequencies of moderate dysplasia and severe dysplasia/carcinoma in situ. The most common histological criteria were the increase in number and size of nucleoli, loss of polarity of the basal cells and variations in cellular size and shape. Classification by the binary system showed that 7% were high-risk lesions. CONCLUSION: All histological criteria for classification of oral epithelial dysplasia recommended by the World Health Organization showed increased frequency as grading increased. Additional criteria seem to be useful in grading oral epithelial dysplasia, such as the presence of normal and abnormal superficial mitotic figures and endophytic epithelial proliferation.

Leucoplasia Verrucosa Proliferativa: Revisão da Literatura com Ênfase no Diagnóstico, Manejo e Tratamento / Proliferative Verrucous Leukoplakia: Literature Review With Emphasis on Diagnosis, Manegement and Treatment

As Desordens Potencialmente Malignas Orais (DPMO) descrevem um grupo de doenças com risco aumentado de desenvolver o Carcinoma Espinocelular (CEC), e a mais comum é a Leucoplasia Oral (LO), que apresenta uma variante agressiva denominada Leucoplasia Verrucosa Proliferativa (LVP). Descrita pela primeira vez em 1985 por Hansen et al., a LVP é considerada uma forma multifocal incomum da doença, com curso clínico agressivo e implacável para malignidade, sem associação com os fatores de risco tradicionais da LO. O diagnóstico e manejo dessa variante é um desafio, pois, além da ausência de biomarcadores comprovados que possam predizer seu curso evolutivo, a subjetividade existente na sua avaliação clínica e histopatológica, faz com que a presença ou grau de Displasia Epitelial Oral (DEO) não consiga determinar se haverá ou não transformação maligna da lesão. O objetivo desse trabalho foi realizar uma Revisão da Literatura Tradicional, focando especificamente nos aspectos sobre diagnóstico, transformação maligna, manejo e tratamento da LVP, variante agressiva da LO. Concluímos que, ainda hoje, não existem biomarcadores que possam predizer o avanço das LO, tornando-se obrigatório o acompanhamento e/ou tratamento de toda e qualquer LO, inclusive os casos de Queratose de significado incerto.

Oral Potentially Malignant Disorders (OPMDs) describe a group of diseases at increased risk of leading to Squamous Cell Carcinoma (SCC). The most common is Oral Leukoplakia (OL), which presents itself through an aggressive variant known as Proliferative Verrucous Leukoplakia (PVL). First described in 1985 by Hansen et al., PVL is considered an uncommon multifocal form of the disease, with an aggressive and relentless clinical course towards malignancy, and lacks association with traditional OL risk factors. The diagnosis and management of this disease form posits a significant challenge since, in addition to the absence of proven biomarkers that can predict its evolutionary course, the subjectivity existing in its clinical and histopathological evaluation means that the presence or degree of Oral Epithelial Dysplasia (OED) is not enough to determine whether or not the lesion will undergo a malignant transformation. The objective of this work was to carry out a Traditional Literature Review focused specifically on aspects of diagnosis, malignant transformation, management and treatment of PVL, an aggressive variant of OL. Our conclusion is that, to this day, there are no biomarkers able to predict the progress of OL, making it necessary to monitor and/or treat all OL cases, including cases of Keratosis of unknown significance.

Oral potentially malignant disorders: clinical-pathological study of 684 cases diagnosed in a Brazilian population

BACKGROUND: The frequency and distribution of oral potentially malignant disorders (OPMD) may vary among dif-ferent populations. The aim of the present study was to evaluate the clinical-pathological characteristics of OPMD diagnosed in a Brazilian oral pathology laboratory over a period of 11 years. MATERIAL AND METHODS: All cases diagnosed as leukoplakia, speckled leukoplakia, erythroplakia, and actinic chei-litis from 2005 to 2015 were analyzed. Clinical information was obtained from laboratory forms and histological information was obtained from histological slides stained with hematoxylin and eosin. RESULTS: the final sample was comprised of 684 cases, of which 292 were males and 392 were females. The mean age was 58 years. The anatomical site most often involved was the lateral border of the tongue (23%), followed by the lower lip (20%), and by the buccal mucosa/vestibule (18%). Leukoplakia accounted for 82% of the sample (564 cases). The mean size of the leukoplakia and speckled leukoplakia lesions was 13 mm (ranging from 1 to 100 mm) and 15 mm (ranging from 5 to 30 mm), respectively (p = 0.460). Males reported smoking and drinking alcohol more frequently than females (p = 0.001 and p < 0.0001, respectively). In half of the cases, dysplasia was not histo-logically detected, while slight dysplasia was detected in 28% of the cases. The lesions from patients aged from 41 to 80 years presented moderate and severe dysplasia more often than lesions from patients in other age groups. CONCLUSIONS: OPMD were more common in females in their sixties. Females were more frequently affected in all anatomical sites, except for the lips. Leukoplakia lesions were the most common OPMD, followed by actinic cheili-tis. The lateral border of the tongue was the most affected anatomical site. OPMD located in the floor of the mouth/sublingual mucosa and lesions from older patients presented severe epithelial dysplasia with greater frequency

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Dystrophic calcification vs sialolithiasis in a pediactric parotid gland: A case report.

Calcinosis is a connective tissue disorder characterized by ectopic calcification in soft tissues. It is subdivided into: dystrophic, metastatic, idiopathic and iatrogenic calcification. The formation of mineralized material in the salivary glands is a common finding in the daily practice of dentists and other specialists. In most cases, this calcification is a sialolith. However, a type of ectopic calcification termed dystrophic calcification is characterized by inappropriate biomineralization in soft tissues and may be associated with trauma, chronic and localized infection or inflammatory diseases. We report a case of a 9-year-old female patient who complained of small nodules in the left parotid region, which begun two years before. Her main complaint was of recurring periods of worsened symptoms characterized by the exacerbation and symptomatic remission of the gland volume with occasional otolaryngologic infections. This study aims to discuss ectopic dystrophic calcification in the parotid gland associated with recurrent infection in children. Key words:Dystrophic calcification, salivary gland, pediatric pathology.