Rab5C enhances resistance to ionizing radiation in rectal cancer.

Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10-40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation. To better understand the role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, affecting expression of the DNA repair proteins, Ku70 and Ku80, and cell resistance. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells and they should be further investigated. KEY MESSAGES: • Rab5C orchestrates a mechanism of radioresistance in rectal adenocarcinoma cell. • Rab5C modulates EGFR internalization and its relocalization to the nucleus. • In the nucleus, EGFR can modulate the expression of the DNA repair proteins, Ku70 and Ku80. • Rab5C, Ku70, and Ku80 are overexpressed in tumor tissues that contain tumor cells that are resistant to chemoradiation treatment.

Rare case report of an aggressive follicular lymphoid hyperplasia in maxilla.

Follicular lymphoid hyperplasia is a very rare though benign reactive process of an unknown pathogenesis that may resemble a follicular lymphoma, clinically and histologically. Oral reactive follicular hyperplasia (RFH) has been described on the hard or soft palate and at the base of the tongue. We describe here the first case of RFH presenting as an aggressive tumor on the right posterior side of the maxilla in a 24-year-old male patient. The lesion had a clinical evolution of 18 months and was noticed after the surgical extraction of the right third molar, although we cannot assume a cause-effect relation with that surgical event whatsoever. His medical history was unremarkable. Following an incisional biopsy, histological examination revealed lymphoid follicles comprised by germinal centers surrounded by well-defined mantle zones. The germinal centers were positive for Bcl-6, CD10, CD20, CD21, CD23, CD79a, and Ki-67, while negative for Bcl-2, CD2, CD3, CD5, and CD138. The mantle and interfollicular zones were positive for Bcl-2, CD2, CD3, CD5, CD20, and CD138. Both areas were diffusively positive for kappa and lambda, showing polyclonality. The patient underwent a vigorous curettage of the lesion with no reoccurrences at 36 months of follow-up. This case report demonstrates that morphologic and immunohistochemical analyses are crucial to differentiate RFH from follicular lymphoma, leading to proper management.

Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. The generation of conventional treatments has improved, but approximately 50 % of patients with CRC who undergo potentially curative surgery ultimately relapse and die, usually as a consequence of metastatic disease. Our previous findings showed that engagement of the cellular prion protein (PrP(C)) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrP(C) has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrP(C)-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrP(C)-dependent manner and that phosphorylation of the ERK1/2 pathway is a downstream mediator of these effects. Additionally, we show that a HOP peptide with the ability to bind PrP(C) and abolish the PrP(C)-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrP(C)-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC.

Perfil psicopatológico e alterações comportamentais em pacientes com queixa de halitose: uma revisão / Psychopathological profile and behavioral alterations in patients with halitosis complaint: a review

O objetivo do presente trabalho é avaliar, através de uma revisão da literatura, dois aspectos importantes no tratamento do mau hálito: perfil psicopatológico e alterações comporta mentais em pacientes com queixa em ter halitose. Materiais e Métodos: realizou-se consultas a livros sobre o tratamento da halitose e a artigos científicos em bancos de dados on-line (PubMed e Birerne), publicados entre os anos de 1957 e 2014, englobando pacientes com mau hálito e também pacientes que não têm halitose, mas apresentam queixa em tê-la. Síntese de dados: a halitose já foi associada a diversas psicopatologias como transtorno de ansiedade social (TAS), fobia específica, síndrome de referência olfatória, dismorfofobia e transtorno obsessivo compulsivo. Outro aspecto importante mencionado na literatura é que pacientes com queixa em ter halitose frequentemente desenvolvem inúmeras alterações comportamentais devido a, por exemplo, sofrer com o problema por longos períodos sem relatá-lo a ninguém, ou por terem uma forte convicção em ter mau hálito, quando na realidade não o têm. Conclusão: tanto pacientes com halitose real como os que têm queixa em ter mau hálito, porém sem evidências de sua presença, são candidatos ao tratamento da halitose, cujos objetivos essenciais são restabelecer um hálito agradável bem como a segurança dos pacientes. Importantes publicações reforçam ser fundamental que os protocolos de tratamento da halitose incluam uma abordagem psicológica, voltada em especial para o TAS. Para os casos refratários, em que a insegurança dos pacientes é difícil de tratar, há indicação de encaminhamento para psicólogos e/ou psiquiatras visando um tratamento multiprofissional.

The present study aims to analyze through a review of the literature two important aspects of halitosis treatment: psychopathological profile and behavioral alterations in patients with halitosis complaint. Materiais and Methods: it was performed a literature search using books about halitosis treatment and scientific articles from online databases (PubMed and Bireme), published between 1957 and 2014. Reports of patients with bad breath as well as patients with halitosis complaint, with no evidence of having it, were included in the research. Data synthesis: halitosis has been associated with severa I psychopathologies, such as social anxiety disorder (SAD), specific phobia, olfactory reference syndrome, dysmorphophobia and obsessive compulsive disorder. Another important aspect mentioned in the literature is that patients complaining of bad breath often develop behavioral changes due to, e.q, suffer from the problem during long periods without reporting it to anyone, or because they have a strong conviction in having bad breath, when in reality they don't have it Conclusion: Both patients with real halitosis as patients with complaint of bad breath, but without evidences of its presence, are candidates for halitosis treatment, which essential goals are to restore a pleasant breath and patient's security.lmportant publications highlight that halitosis treatment protocols should include a psychological approach, directed especially for SAD. For refractory cases, in which patients' insecurity is difficult to deal with, there is an indication for referral to psychologists and/or psychiatrists targeting for multidisciplinary treatment.

NFκB mediates cisplatin resistance through histone modifications in head and neck squamous cell carcinoma (HNSCC).

Cisplatin-based chemotherapy is the standard treatment of choice for head and neck squamous cell carcinoma (HNSCC). The efficiency of platinum-based therapies is directly influenced by the development of tumor resistance. Multiple signaling pathways have been linked to tumor resistance, including activation of nuclear factor kappa B (NFκB). We explore a novel mechanism by which NFκB drives HNSCC resistance through histone modifications. Post-translational modification of histones alters chromatin structure, facilitating the binding of nuclear factors that mediate DNA repair, transcription, and other processes. We found that chemoresistant HNSCC cells with active NFκB signaling respond to chemotherapy by reducing nuclear BRCA1 levels and by promoting histone deacetylation (chromatin compaction). Activation of this molecular signature resulted in impaired DNA damage repair, prolonged accumulation of histone γH2AX and increased genomic instability. We found that pharmacological induction of histone acetylation using HDAC inhibitors prevented NFκB-induced cisplatin resistance. Furthermore, silencing NFκB in HNSCC induced acetylation of tumor histones, resulting in reduced chemoresistance and increased cytotoxicity following cisplatin treatment. Collectively, these findings suggest that epigenetic modifications of HNSCC resulting from NFκB-induced histone modifications constitute a novel molecular mechanism responsible for chemoresistance in HNSCC. Therefore, targeted inhibition of HDAC may be used as a viable therapeutic strategy for disrupting tumor resistance caused by NFκB.

Oestrogens and androgen receptors in oral squamous cell carcinoma.

OBJECTIVE: To investigate the gender-related expressions of androgen (AR), estrogen alpha (ERα) and beta (ERß) receptors and aromatase enzyme in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A total of 60 cases of OSCC (30 from males and 30 from females) were retrieved and submitted to immunohistochemistry. Also, steroid expression was studied in two OSCC cell lines using Western blotting and immunofluorescence. RESULTS: Immunohistochemistry demonstrated that ERß was expressed in almost 40% of the cases and AR in 26%. Aromatase enzyme and ERα were less commonly expressed. Only AR presented statistically significant differences between genders. Western blotting and immunofluorescence analysis demonstrated that ERß was abundantly expressed in the nuclei of both cell lines and aromatase enzyme presented a cytoplasmic expression. CONCLUSION: The detection of steroid hormones, especially ERß, can indicate a role of these proteins in the process of carcinogenesis of some OSCC. Further studies of the mechanisms involved may provide important biological information regarding therapeutic approaches.

Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma.

BACKGROUND: Celecoxib, a non-steroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2 (COX-2), has shown an important anticarcinogenic effect for the treatment of squamous cell carcinoma. The use of COX-2 inhibitors has effectively inhibited the growth of Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines, while a recent phase 1 trial demonstrated good response rate of cancer cells to this drug with minimal toxicity. Possible targets of celecoxib include proteins involved in cell proliferation and apoptosis control. Additionally, celecoxib antitumoral activity has been linked with a COX-2-independent event. METHODS: To better understand which cellular mechanisms are targeted by celecoxib, its effects upon the Akt signaling pathway using two different HNSCC cell lines were analyzed through cell viability assay, immunofluorescence, and Western blotting. RESULTS: The results showed decreased levels of Cyclin D1 and pAkt protein expression in vitro. The number of viable cells was also diminished after celecoxib treatment. CONCLUSION: As Akt pathway seems to be a valuable target for the HNSCC therapy, the results presented herein confirm that celecoxib can be considered as an alternative adjuvant drug for HNSCC treatment.

Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway.

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Head and neck cancer patients receiving LLLT for oral mucositis, for example, might have remaining tumor cells that could be stimulated by LLLT. This study demonstrated that LLLT (GaAlAs--660 nm or 780 nm, 40 mW, 2.05, 3.07 or 6.15 J/cm²) can modify oral dysplastic cells (DOK) and oral cancer cells (SCC9 and SCC25) growth by modulating the Akt/mTOR/CyclinD1 signaling pathway; LLLT significantly modified the expression of proteins related to progression and invasion in all the cell lines, and could aggravate oral cancer cellular behavior, increasing the expression of pAkt, pS6 and Cyclin D1 proteins and producing an aggressive Hsp90 isoform. Apoptosis was detected for SCC25 and was related to pAkt levels.

Inhibition of histone deacetylase impacts cancer stem cells and induces epithelial-mesenchyme transition of head and neck cancer.

The genome is organized and packed into the nucleus through interactions with core histone proteins. Emerging evidence suggests that tumors are highly responsive to epigenetic alterations that induce chromatin-based events and dynamically influence tumor behavior. We examined chromatin organization in head and neck squamous cell carcinoma (HNSCC) using acetylation levels of histone 3 as a marker of chromatin compaction. Compared to control oral keratinocytes, we found that HNSCC cells are hypoacetylated and that microenvironmental cues (e.g., microvasculature endothelial cells) induce tumor acetylation. Furthermore, we found that chemical inhibition of histone deacetylases (HDAC) reduces the number of cancer stem cells (CSC) and inhibits clonogenic sphere formation. Paradoxically, inhibition of HDAC also induced epithelial-mesenchymal transition (EMT) in HNSCC cells, accumulation of BMI-1, an oncogene associated with tumor aggressiveness, and expression of the vimentin mesenchymal marker. Importantly, we observed co-expression of vimentin and acetylated histone 3 at the invasion front of human HNSCC tumor tissues. Collectively, these findings suggest that environmental cues, such as endothelial cell-secreted factors, modulate tumor plasticity by limiting the population of CSC and inducing EMT. Therefore, inhibition of HDAC may constitute a novel strategy to disrupt the population of CSC in head and neck tumors to create a homogeneous population of cancer cells with biologically defined signatures and predictable behavior.

The determinants of head and neck cancer: Unmasking the PI3K pathway mutations.

Studies attempting to identify and understand the function of mutated genes and deregulated molecular pathways in cancer have been ongoing for many years. The PI3K-PTEN-mTOR signaling pathway is one of the most frequently deregulated pathways in cancer. PIK3CA mutations are found 11%-33% of head and neck cancer (HNC). The hotspot mutation sites for PIK3CA are E542K, E545K and H1047R/L. The PTEN somatic mutations are in 9-23% of HNC, and they frequently cluster in the phosphatase domain of PTEN protein. PTEN loss of heterozygosity (LOH) ranges from 41%-71% and loss of PTEN protein expression occurs in 31.2% of the HNC samples. PIK3CA and PTEN are key molecules in the PI3K-PTEN-mTOR signaling pathway. In this review, we provided a comprehensive overview of mutations in the PI3K-PTEN-mTOR molecular circuitry in HNC, including PI3K family members, TSC1/TSC2, PTEN, AKT, and mTORC1 and mTORC2 complexes. We discussed how these genetic alterations may affect protein structure and function. We also highlight the latest discoveries in protein kinase and tumor suppressor families, emphasizing how mutations in these families interfere with PI3K signaling. A better understanding of the mechanisms underlying cancer formation, progression and resistance to therapy will inform selection of novel genomic-based personalized therapies for head and neck cancer patients.

Difficulty in diagnosing oral paracoccidioidomycosis after topical nystatin usage.

Paracoccidioidomycosis (PCM) is caused by a dimorphic fungus called Paracoccidioides brasiliensis and is a disseminated, systemic disorder that involves the lungs and other organs but presents characteristic oral lesions as the prominent feature. This article reports an unusual case of a 56-year-old man who had symptomatic granulomatous lesions in the oral cavity. The patient had received a nystatin-based treatment that masked the presence of fungi and made the diagnosis of PCM difficult. Although nystatin is normally used to treat oral fungal infections such as candidiasis, its topical usage is not appropriate for management of PCM. Once the patient received the correct treatment, he demonstrated a full recovery.

Oestrogen receptor ß in adenoid cystic carcinoma of salivary glands.

AIMS: This study aimed to describe the expression of oestrogen receptor (ER)α, ERß and aromatase in salivary gland adenoid cystic carcinoma (ACC). METHODS AND RESULTS: ERα, ERß and aromatase expression was analysed by immunohistochemistry in tissue microarray blocks from 38 cases of ACC and seven normal salivary glands. The intracellular localization and amount of total protein expression were investigated by immunofluorescence and western blotting in an ACC cell line. Western blotting analysis showed overexpression of ERα, ERß and aromatase in the ACC cell line; however, with immunofluorescence, only ERß was shown to be expressed in the nucleus. Immunohistochemistry revealed positive nuclear expression of ERß, positive cytoplasmic expression of aromatase and a lack of ERα expression as compared with normal salivary glands. CONCLUSIONS: The nuclear expression of ERß indicates that oestrogen may be active in ACC and possibly able to mediate E2-targeted gene transcription. This study strongly suggests that ERß may be involved in tumour progression, playing a role in tumour development, and thus corroborating the indication for ER antagonists in the clinical control of ACC. This study opens a new perspective on the potential use of anti-oestrogens and aromatase inhibitors as therapeutic agents against ACC.

Is it safe to utilize in vitro reconstituted human oral epithelium? An oncogenetic pathway study.

Cell therapy is a therapeutic strategy used to replace or repair damaged tissue. The epithelium transplantation of cultivated keratinocytes has been applied to several modalities of reconstruction, like oral, urethra and ocular surface. Life and death signals work coordinately to ensure cellular quality control and the viability of an organism. The aim of this study is to verify that culture conditions did not induce genetic mutations through the analysis of the key genes: pAKT, Pten, p53 and MDM2 and investigate the presence of the related proteins in human oral keratinocytes obtained by primary culture and in vitro cultivated. Formalin fixed and paraffin embedded tissues from the oral cavity were utilized as control for normal expression of the related markers and two oral squamous cell carcinoma cell lines provided the expression pattern of the proposed markers in the event of cellular transformation. Akt, PTEN, p53 and MDM2 immunohistochemistry and Western-Blotting analyzes were performed. The results showed the expression levels and intracellular localizations of the four proteins evaluated. These analyzes confirmed that the produced in vitro epithelium is bio-compatible for its utilization as reconstruction and reparatory tissue, however further analyses and additional research on other biomarkers should be performed to analyse the long term engraftment of transplantable primary culture of oral keratinocytes and the long term resistance to cellular transformation.

An in vitro study showing the three-dimensional microenvironment influence over the behavior of head and neck squamous cell carcinoma.

OBJECTIVES: The Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth worldwide. The mechanisms of growth, invasion and metastasis of this pathology are extensively studied and generally related to specific variations in signaling pathways like the PI3K-Akt; however most of these competent studies have been performed bidimensionally, which may hide important questions. This study sought to analyze the influence of the microenvironment upon the behavior of HNSCC. STUDY DESIGN: The status of pAkt, NF-κB and Cyclin D1 proteins was accessed through immunofluorescence and western blot methods in HNSCC cell lines originating from tongue, pharynx and metastatic lymph node when submitted to a three-dimensional culture model utilizing a matrix system. A bidimensional culture model (monolayer) was used as control. RESULTS: The HNSCC cell lines cultured three-dimensionally exhibited a growth pattern characterized by small isolated islands, different from the control group. When the three-dimensional model was applied, two of the studied cell lines showed the same expression pattern as the bidimensional model regarding nuclear or cytoplasmatic localization, as well as reduction of all protein levels; however, the cell line originated from tongue, which specially has the epidermal growth factor receptor constitutively activated, demonstrated nuclear translocation of pAkt and also an increase in the levels of Cyclin D1. CONCLUSIONS: The results suggest the influence of the microenvironment upon the behavior of HNSCC cells due to the changed expression of proteins related to tumor growth and cellular invasion. Furthermore, intrinsically genetic conditions also played important roles over the cells, despite the culture model employed.

O envolvimento da remodelação da cromatina no controle do comportamento agressivo dos carcinomas epidermoides de cabeça e pescoço / The involvement of chromatin remodeling in the control of head and neck squamous cell carcinoma behavior

Modificações nas histonas são conhecidas por regular a estrutura conformacional da cromatina e a expressão gênica em células adultas e células-tronco pluripotentes. Tem sido postulado que a acetilação e deacetilação das histonas podem influenciar a expressão de genes envolvidos na iniciação, progressão e metástase tumoral, além de contribuir para o desenvolvimento de resistência à quimioterapia. Assim, buscou-se avaliar a influência das modificações nas histonas sobre a biologia do carcinoma epidermoide de cabeça e pescoço (CECP) e sua respectiva subpopulação de células semelhantes às células-tronco (CSC). Inicialmente, foi checado os níveis de acetilação da histona H3 (membro das histonas nucleares associado à compactação da cromatina) em um painel representativo de linhagens celulares de CECP. Posteriormente, para estudar a influência do estroma tumoral no padrão de acetilação da histona H3, o microambiente do tumor foi mimetizado através da utilização de meio condicionado derivado do cultivo de fibroblastos e cultura primária de células endoteliais humanas. Além disso, validamos esses resultados in vitro por meio de amostras humanas de CECP. Finalmente, a acetilação e deacetilação da cromatina foi induzida, respectivamente, pela administração dos inibidores das enzimas histona deacetilase tricostatina A (TSA) e histona acetiltransferase curcumina, em linhagens celulares de CECP. Foi feita a análise da formação de esferas (ensaio funcional de células-tronco), juntamente com a verificação dos níveis de ALDH, marcador de células-tronco (citometria de fluxo - FACS), além da determinação do índice de proliferação tumoral (Ki-67) e realização dos ensaios de invasão e migração celular. Linhagens celulares de CECP apresentaram níveis baixos de acetilação da histona H3 e demonstraram capacidade de retenção de uma subpopulação de CSC. Apenas o meio condicionado de células endoteliais humanas foi capaz de alterar a conformação da cromatina, uma vez que induziu o aumento da acetilação da histona H3. Interessantemente, foi também notado um concomitante aumento da agressividade de linhagens celulares de CECP (aumento dos níveis de BMI-1 e vimentina). Esses resultados foram confirmados em amostras humanas de CECP que mostraram, apenas no fronte de invasão, células com cromatina acetilada. Curiosamente, essas mesmas células também expressaram vimentina. Os tratamentos com TSA e curcumina resultaram na diminuição significativa da subpopulação de CSC, interrompendo a formação de esferas e reduzindo os níveis de ALDH. Além disso, o tratamento com curcumina mostrou resultados muito interessantes, uma vez que gerou uma redução evidente da invasão celular e impactou por completo o potencial de migração tumoral, sendo nesse sentido mais eficiente que a cisplatina, droga antineoplásica bem estabelecida. Por outro lado, o tratamento com TSA induziu a transição epitélio-mesenquimal nas linhagens celulares de CECP, detectada pelo aumento da expressão de vimentina e indução de um fenótipo fusiforme, juntamente com o aumento da invasão tumoral e os níveis de BMI-1.

Histone modifications are known to regulate chromatin conformation structure and gene expression in adult cells and pluripotent stem cells. It has been postulated that histone acetylation and deacetylation could influence the expression of genes involved in cancer initiation, progression, metastasis, and development of resistance to chemotherapies. Here, we sought to evaluate the influence of histone modifications over the biology of head and neck squamous cell carcinoma (HNSCC) and its stem cell-like subpopulation (CSC). Initially, we checked the status of histone H3 acetylation (a member of the core histones associated to chromatin compaction) in a representative set of HNSCC cell lines. Subsequently, to analyze the influence of tumor stroma over the histone H3 acetylation, we mimicked the tumor microenvironment by using conditioned medium from fibroblasts and primary human endothelial cells. Further we validated these in vitro findings through human samples of HNSCC. Finally, we induced chromatin acetylation and deacetylation by the administration of the histone deacetylase inhibitor trichostatin A (TSA) and histone acetyltransferase inhibitor curcumin, respectively, in HNSCC cell lines. The analysis of spheres formation (stem cell functional assay), along with the levels of stem cells marker ALDH (showed by flow cytometry - FACS), tumor proliferation index (Ki-67), invasion and migration cellular potencial were verified. HNSCC cell lines showed lower levels of histone H3 acetylation and ability to retain a subpopulation of CSC.

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.

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.

The immunohistochemical profile of oral inflammatory myofibroblastic tumors.

OBJECTIVE: The aim of this study was to demonstrate the immunohistochemical profile of oral inflammatory myofibroblastic tumors (IMTs) along with morphologic analysis. STUDY DESIGN: Three cases diagnosed as oral IMTs were selected to compile an immunohistochemical panel constituted by calponin, caldesmon, Bcl-2, desmin, fibronectin, CD68, Ki-67, S100, anaplastic lymphoma kinase (ALK), α-smooth muscle actin, cytokeratins AE1/AE3, muscle-specific actin, CD34, and vimentin. An oral squamous cell carcinoma with a focal area of desmoplastic stroma was used as control for the stained myofibroblastic cells. RESULTS: All oral IMTs were positive for calponin, revealing a strong and diffuse expression in the spindle-shaped cells. The lesions were also positive for vimentin (3/3), fibronectin (3/3), α-smooth muscle actin (3/3), and muscle-specific actin (1/3) and negative for h-caldesmon, Bcl-2, desmin, CD68, Ki-67, S100, ALK, cytokeratins AE1/AE3, and CD34. CONCLUSIONS: Within the results encountered, the present panel should be of great assistance in the diagnosis of oral IMTs.

Análise da expressão das proteínas ß-catenina e caderina-E em linhagens celulares de carcinoma epidermoide de cabeça e pescoço / Analysis of ß-catenin and E-cadherin protein expression in head and neck squamous cell carcinoma cell lines

O carcinoma epidermoide corresponde a 95% das neoplasias malignas da cavidade oral, sendo seu mecanismo de invasão pouco conhecido. As células dessa neoplasia sofrem alterações genéticas e epigenéticas que as deixam com um caráter mais agressivo e, consequentemente, invasivo. Algumas vias de sinalizaçãoexercem papel importante sobre essas alterações. entre elas, a via do Wnt, em que se encontra um complexo formado por ß-catenina, um proto-oncogene e caderina-E, uma das principais moléculas de adesão do epitélio. Esse complexo torna-se responsável pela adesão entre as células e também por controlar a diferenciação morfológica e a proliferação celular. Assim, o propósito deste estudo foi analisar a expressão das proteínas ß-catenina e caderina-E em linhagens celulares derivadas de carcinoma epidermoide de cabeça e pescoço (CECP) e verificar a influência da matriz extracelular na expressão dessas proteínas. Os resultados mostraram que houve variação na expressão de ß-catenina e de caderina-E, dependendo da linhagem estudada, bem como do ambiente de cultivo celular empregado. Portanto, as proteínas ß-catenina e caderina-E foram expressas no CECP e a matriz extracelular foi capaz de alterar a expressão dessas proteínas

Células-tronco de origem dental - populações e características / Dental stem cells - populations and characteristics

Células-tronco adultas já foram encontradas em uma variedade de tecidos humanos. Nos tecidos dentais essas células já foram isoladas da polpa de dentes permanentes e decíduos, do ligamento periodontal, da papila apical e do folículo dentário. A engenharia de tecidos mostra a utilização das células-tronco dentais como futura alternativa promissora para tratamentos restauradores. A construção de estruturas complexas como polpa e periodonto, por exemplo, poderá revolucionar a odontologia moderna. De modo geral, as células-tronco de origem dental são de fácil acesso e podem ser caracterizadas com base em propriedades específicas. Esta revisão de literatura trouxe um breve panorama sobre as células-tronco de origem dentária, mostrando as principais diferenças encontradas entre suas populações e discutindo conceitos básicos a seu respeito