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BACKGROUND/AIM: Several strategies have been developed for tooth fragment reattachment following fracture. Although many techniques have been reported, there is no consensus on which one has the best results in terms of the bond strength between the fragment and the dentin over time. The aim of this study was to assess the currently reported tooth fragment reattachment techniques for fractured crowns of anterior teeth. MATERIALS AND METHODS: The PubMed, LILACS, Web of Science, Cochrane, and Scopus databases were searched in October 2016, and the search was updated in February 2017. A search of the gray literature was performed in Google Scholar and OpenGrey. Reference lists of eligible studies were cross-checked to identify additional studies; gray literature and ongoing trials were investigated. Two authors assessed studies to determine inclusion and undertook data extraction. Case reports/series of three or more cases, cross-sectional studies, cohort studies, and in vivo clinical trials in all languages were included. RESULTS: Five articles remained after screening. These studies predominantly reported on fragment reattachment with composite resin and resin cement. There was little consistency among the studies in regard to the technique used for tooth fragment reattachment and length of the follow-up period. CONCLUSIONS: According to the evidence found in the studies included in this review, simple tooth fragment reattachment was the preferred reattachment technique. An increase in the bond strength between tooth fragment and dentin was observed when an intermediate material was used. Further investigation is needed, using standard follow-up periods and larger samples.

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AIM: To perform a meta-analysis to assess whether the presence of cancer-associated fibroblasts (CAF) is a prognostic marker of oral squamous cell carcinomas (OSCC). METHODS: Immunohistochemical studies assessing the prognostic relevance of CAF (alpha smooth muscle actin (α-SMA)-positive fibroblasts) in patients with OSCC were systematically reviewed using Cochrane, Lilacs, PubMed, Scopus, and Web of Science databases. The outcomes assessed were overall survival (OS) and disease-free survival (DFS). The meta-analysis was performed using the random- and fixed-effects model with adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures. The methodological quality of the included studies was assessed using the Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) tool, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: The presence of high levels of CAF in the stroma of OSCC predicted shortened time to DFS (HR = 3.32, 95% CI: 2.09-5.26, P < .00001) and an overall decrease in survival (HR: 2.16, 95% CI: 1.60-2.92, P < .00001). Moreover, high presence of CAF was frequently reported in association with parameters that worsen the prognosis in OSCC, including advanced disease stage (TNM classification), recurrence, tumor grade, depth of invasion, vascular, lymphatic and neural invasion, and extranodal metastatic spread. CONCLUSION: The presence of CAF, as assessed by α-SMA-positive fibroblasts in the stroma, indicates poor prognosis in patients with OSCC.

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BACKGROUND: Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients. METHODS: The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users. RESULTS: Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I2=40%). CONCLUSION: Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions.

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The aim of this study was to systematically review the literature about the capability of CBCT images to identify individuals with low bone mineral density (BMD). As the literature is scarce regarding this topic, the purpose of this systematic review is also to guide future research in this area. A detailed search was performed in five databases without restrictions of time or languages. Additionally, a grey literature search was conducted. The Quality Assessment Tool for Diagnostic Accuracy Studies-2 was applied to evaluate the methodological design of selected studies. With the inclusion of only six studies, the evidence is limited to endorse the use of CBCT assertively as a diagnostic tool for low BMD. All of the three studies that analyzed radiomorphometric indices found that the linear measurements of the mandibular inferior cortex were lower in osteoporotic individuals. CBCT-derived radiographic density vertebral and mandibular measurements were also capable for differentiating individuals with osteoporosis from individuals with normal BMD. The analysis of the cervical vertebrae showed high accuracy measurements. This systematic review indicates a scarcity of studies regarding the potential of CBCT for screening individuals with low BMD. However, the studies indicate that radiomorphometric indices and CBCT-derived radiographic density should be promising tools for differentiating individuals with osteoporosis from individuals with normal BMD.

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The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

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Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.

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Abstract The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

Resumo O câncer de boca e de orofaringe emerge como o 6º tipo de câncer mais comum no mundo. O tratamento pode envolver cirurgia, quimioterapia e radioterapia. Mais de 50% das drogas com atividade de combate ao câncer foram isoladas de fontes naturais, tais como a Catharanthus roseus e a epipodofilotoxina, isolada de Podophyllum. O maior desafio é maximizar o controle da doença, enquanto minimiza a morbidade e toxicidade para os tecidos normais circundantes. O Erythroxylum suberosum é uma planta comum no bioma Cerrado brasileiro e é popularmente conhecida como "cabelo-de-negro". O objetivo deste estudo foi avaliar a citotoxicidade dos extratos da planta Erythroxylum suberosum do bioma Cerrado brasileiro, associados à radioterapia em linhagens celulares humanas de carcinomas de língua e de hipofaringe. As células foram tratadas com os extratos aquoso, etanólico e hexânico do Erythroxylum suberosum e irradiadas com 4 Gy, 6 Gy e 8 Gy. A citotoxidade foi avaliada pelo ensaio de MTT e a absorvância foi medida a 570 nm em uma leitora Beckman. A cisplatina, quimioterápico padrão, foi utilizada como controle positivo. O uso de extratos de Erythroxylum suberosum mostrou potencial efeito radiosensibilizante in vitro no câncer de cabeça e pescoço. O efeito da citotoxicidade nas linhagens foi de forma não seletiva e muito semelhante ao efeito da quimioterapia padrão. O extrato aquoso de Erythroxylum suberosum, combinado com radioterapia, foi o extrato mais citotóxico para os carcinomas de língua e hipofaringe, associados à radioterapia.

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This in vitro study evaluated in fibroblast cultures the direct cytotoxicity of universal, self-etching and etch-and-rinse adhesive systems according to the polymerization time. Paper discs were impregnated with adhesives and light-cured (10, 20 or 40 s). The discs were then immersed in culture medium to obtain the eluates for the experimental groups (A1-Single Bond 2; A2-Scotchbond Multi-purpose; A3-Clearfil SE Bond; A4 Scotchbond Universal). As a negative control, paper discs were immersed in culture medium only. After 24 h or 7 days, the eluate obtained was applied on fibroblast culture. Cell viability, cell morphology, membrane damage and the presence of residual monomers were evaluated by MTT assay, SEM, flow cytometry and high-performance liquid chromatography (HPLC), respectively. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests (=0.05). All adhesive systems significantly reduced 33-51% cell metabolism when compared to the negative control, regardless of polymerization time, storage period and adhesive system. Moreover, the adhesives caused intense morphological alterations and cell membrane damage. Toxicity was directly related to the presence of residual monomers in the eluates. Residual monomers and additional components are capable of reducing mitochondrial activity, causing morphological alterations and disruption of the cell membrane in fibroblasts, regardless of the polymerization time. This study highlights that despite the more complex composition of the universal adhesive system, its biological response was not more toxic when compared with other systems, even when the shortest polymerization time was tested in cell culture.

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This in vitro study evaluated in fibroblast cultures the direct cytotoxicity of universal, self-etching and etch-and-rinse adhesive systems according to the polymerization time. Paper discs were impregnated with adhesives and light-cured (10, 20 or 40 s). The discs were then immersed in culture medium to obtain the eluates for the experimental groups (A1-Single Bond 2; A2-Scotchbond Multi-purpose; A3-Clearfil SE Bond; A4 Scotchbond Universal). As a negative control, paper discs were immersed in culture medium only. After 24 h or 7 days, the eluate obtained was applied on fibroblast culture. Cell viability, cell morphology, membrane damage and the presence of residual monomers were evaluated by MTT assay, SEM, flow cytometry and high-performance liquid chromatography (HPLC), respectively. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests (=0.05). All adhesive systems significantly reduced 33-51% cell metabolism when compared to the negative control, regardless of polymerization time, storage period and adhesive system. Moreover, the adhesives caused intense morphological alterations and cell membrane damage. Toxicity was directly related to the presence of residual monomers in the eluates. Residual monomers and additional components are capable of reducing mitochondrial activity, causing morphological alterations and disruption of the cell membrane in fibroblasts, regardless of the polymerization time. This study highlights that despite the more complex composition of the universal adhesive system, its biological response was not more toxic when compared with other systems, even when the shortest polymerization time was tested in cell culture.

O presente estudo in vitro avaliou a citotoxicidade direta dos sistemas adesivos convencionais, autocondicionantes e universais de acordo com o tempo de polimerização em cultura de fibroblastos. Discos de papel foram impregnados com adesivos e fotoativados (10, 20 e 40 s). Os discos foram posteriormente imersos em meio de cultura para obtenção dos eluatos dos grupos experimentais (A1-Single Bond 2; A2-Scotchbond Multi-purpose; A3-Clearfil SE Bond; A4 Scotchbond Universal). Para o controle negativo, os discos de papel foram imersos somente em meio de cultura. Após 24 h ou 7 dias, o eluato obtido foi aplicado na cultura de fibroblastos. O metabolismo celular, morfologia, dano de membrana e presença de monômeros residuais foram avaliados por teste de MTT, MEV, citometria de fluxo e HPLC, respectivamente. Os dados foram analisados estatisticamente por Kruskal-Wallis e Mann-Whitney. Todos os sistemas adesivos reduziram significativamente o metabolismo celular em 33 a 51% quando comparados ao grupo controle, independente do tempo de polimerização, período de armazenamento e tipo de sistema adesivo. O eluato do adesivos causou ainda intensas alterações morfológicas e danos à membrana celular. A toxicidade foi diretamente relacionada à presença de monômeros residuais nos eluatos experimentais. Monômeros residuais e componentes adicionais dos sistemas adesivos foram capazes de reduzir a atividade mitocondrial, causar alterações morfológicas e danos à membrana citoplasmática de fibroblastos, independente do tempo de polimerização. Esse estudo evidencia que apesar de uma composição mais complexa do sistema adesivo universal, sua resposta biológica não apresentou maior toxicidade quando comparado aos demais sistemas, mesmo no menor tempo de polimerização quando testados em cultura celular.

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OBJECTIVES: Antineoplastic effects of molecules derived from plants have recently gained increasing attention as an additive to traditional therapies. The aim of this study was to evaluate the cytotoxic activity of plant extracts from the Brazilian Cerrado biome associated with radiotherapy in head and neck carcinoma cells (HNSCC). MATERIALS AND METHODS: Fifteen extracts derived from five Cerrado plants were tested in HNSCC cell lines (SCC-25, SCC-9, FaDu) and keratinocyte cells (HaCat). Cell cytotoxicity of extracts and association extract/radiation (2Gy/min) was assessed by MTT assay. Cisplatin (50 µg/mL) was used as a positive control. Extracts with the major cytotoxic activity were selected and their IC50 concentrations were defined. Apoptosis was assessed using flow cytometric analysis. RESULTS: Ten isolated extracts resulted in moderate cytotoxicity (>20 and ≤ 50 % of viable cells), while three extracts induced severe cytotoxic effects (≤ 20 % of viable cells). Plant extracts treatment improved radiotherapy cytotoxicity in all cell lines. Although plant extracts are not as potent as cisplatin plus radiation, in FaDu cells, seven extracts associated with irradiation showed cytotoxic activity similar or better than the association of cisplatin and radiation. Hexanic extract of Erythroxylum daphinites could induce apoptosis in oral cancer cells; however, necrosis was the prevalent kind of death in FaDu cells treated with hexanic extract of Erythroxylum suberosum. CONCLUSIONS: Pre-treatment of HNSCC cells with the extract derived from Cerrado plants followed by irradiation induced a supra-additive cytotoxic effect. CLINICAL RELEVANCE: This study highlights the potential biological relevance of the Cerrado biome when associated with traditional therapy for cancer.

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