Metabolic state of glioma stem cells and nontumorigenic cells

Gliomas contain a small number of treatment-resistant glioma stem cells (GSCs), and it is thought that tumor regrowth originates from GSCs, thus rendering GSCs an attractive target for novel treatment approaches. Cancer cells rely more on glycolysis than on oxidative phosphorylation for glucose metabolism, a phenomenon used in 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography imaging of solid cancers, and targeting metabolic pathways in cancer cells has become a topic of considerable interest. However, if GSCs are indeed important for tumor control, knowledge of the metabolic state of GSCs is needed. We hypothesized that the metabolism of GSCs differs from that of their progeny. Using a unique imaging system for GSCs, we assessed the oxygen consumption rate, extracellular acidification rate, intracellular ATP levels, glucose uptake, lactate production, PKM1 and PKM2 expression, radiation sensitivity, and cell cycle duration of GSCs and their progeny in a panel of glioma cell lines. We found GSCs and progenitor cells to be less glycolytic than differentiated glioma cells. GSCs consumed less glucose and produced less lactate while maintaining higher ATP levels than their differentiated progeny. Compared with differentiated cells, GSCs were radioresistant, and this correlated with a higher mitochondrial reserve capacity. Glioma cells expressed both isoforms of pyruvate kinase, and inhibition of either glycolysis or oxidative phosphorylation had minimal effect on energy production in GSCs and progenitor cells. We conclude that GSCs rely mainly on oxidative phosphorylation. However, if challenged, they can use additional metabolic pathways. Therefore, targeting glycolysis in glioma may spare GSCs

Prevalência de achados sugestivos de papilomavírus humano (HPV) em biópsias de carcinoma espinocelular de cavidade oral e orofaringe: estudo preliminar Prevalence of histological findings of human papillomavirus (HPV) in oral and oropharyngeal squamous cell carcinoma biopsies: preliminary study

O papilomavírus humano (HPV) é universalmente aceito como agente causal do câncer de colo uterino e, recentemente, vem se especulando sobre sua possível relação com câncer oral e de orofaringe. O carcinoma espinocelular (CEC) oral representa 90% de todos os tumores malignos que afetam a cavidade bucal. Estudos sobre a prevalência de HPV em pacientes com CEC variam de 0 a 100%. O efeito citopático viral mais conhecido é a coilocitose, considerado "critério maior" na infecção pelo HPV do ponto de vista histopatológico. OBJETIVO: O objetivo deste estudo foi verificar a prevalência de achados sugestivos de HPV - coilocitose - em CEC oral e de orofaringe. FORMA DE ESTUDO: coorte transversal. MATERIAL E MÉTODO: Foram examinadas no microscópio 20 lâminas com o diagnóstico de CEC de cavidade oral ou orofaringe sendo que em 15 delas foi encontrada coilocitose, correspondendo a 75%. RESULTADO: Apesar de termos conhecimento que o método com maior sensibilidade atual para pesquisa de HPV ser a reação de polimerase em cadeia (PCR), iniciamos esta pesquisa com a investigação de coilocitose, o que é muito sugestivo de infecção por HPV. CONCLUSÃO: O estudo em questão trata-se de um projeto-piloto pois será dada continuidade a esta pesquisa através da realização de PCR a fim de confirmar a alta prevalência de infecção por HPV em CEC oral e de orofaringe.<br>Human papillomavirus (HPV) is considered to be an etiologic agent of cervical cancer and, recently its relation to oral and oropharyngeal cancer has also been investigated. Oral squamous cell carcinoma (SCC) represents 90% of all malignant tumors that affect the oral cavity. The prevalence of HPV in patients with SCC ranges from 0 to 100%. The most known viral cytopathic effect is koilocytosis, considered to be a major characteristic of HPV infection. AIM: The aim of this study was to verify the prevalence of some peculiar characteristics of HPV - koilocytosis - in oral and oropharyngeal SCC. STUDY DESIGN: transversal cohort. MATERIAL AND METHOD: Twenty slides with oral and/or oropharyngeal SCC were examined under microscopy. RESULTS: in 15 of them, koilocytosis was found, amounting to 75%. Although we know that polymerase chain reaction (PCR) is the method with the best sensitivity for HPV detection, we began this research looking for koilocytosis, which is highly suggestive of HPV infection. CONCLUSION: This study is a trial project and we will continue this research with PCR measures to confirm this high prevalence of HPV infection in oral and oropharyngeal SCC

Oral Calcifying Fibrous Pseudotumor: Case Analysis and Review

Calcifying fibrous pseudotumor (CFT) is a rare distinct soft-tissue lesion characterized histologically by lymphoplasmacytic aggregates in a rich collagenized background with abundant psammomatous and dystrophic calcifications. Occurring most often in children and young adults, CFTs are clinically benign lesions that can form over a broad anatomic distribution, including in subcutaneous and deep soft tissues, as well as in serosal and visceral locations. The cause and mechanisms of pathogenesis of CFT are unknown. Simple excision with a margin of normal tissue is the treatment of choice. The risk for local recurrence is low. In this article, we describe a case of CFT in a 29-year-old woman with a 7-cm mass on the right upper gingiva and hard palate, discuss the differential diagnosis with other oral spindle cell lesions, such as, desmoid fibromatosis, nodular fasciitis, inflammatory myofibroblastic tumors, solitary fibrous tumor and also review the recent literature on this rare benign entity