Bilateral peripheral facial palsy: A rare case report.

Peripheral facial palsy (PFP) is an inflammation of the facial nerve, which paralyses the face unilaterally or bilaterally, causing pain and discomfort to the patient. PFP affects the lives of compromised individuals not only due to the loss of essential facial functions (smiling, blinking, talking) but also their emotional state. When the face is paralysed, the lost ability to animate the face can be devastating and is often associated with depression, social isolation, and reduced quality of life. Bilateral involvement is extremely rare and as it occurs in unilateral cases, a thorough clinical and laboratory evaluation must be carried out to determine the etiology of the disease, which can be idiopathic, infectious, neoplastic, traumatic, or iatrogenic. In addition to these, in times of the pandemic, coronavirus disease 2019 (COVID-19) and the vaccine against it should be considered as possible causal factors. Drug therapy and physiotherapy are indicated to recover facial movements. The aim of the present study was to report a case of bilateral peripheral facial palsy due to herpes simplex virus reactivation in a 20-year-old female patient.

Non-Hodgkin lymphoma of a palate: A case report of a highly destructive lesion.

Non-Hodgkin lymphoma (NHL) is a haematolymphoid neoplasm that can affect nodal and extra-nodal sites. It is a rare disease in the oral cavity, accounting for only 2% of all extra-nodal lymphomas. Its aetiology is multi-factorial, being strongly associated with viral infections. The average age group most affected is 66 years old, with a slight predilection for males. The most common histological sub-type in the oral cavity is diffuse large B-cell lymphoma, with Waldeyer's ring being the most affected site in the nodal form, and extranodally, it may involve the tongue, hard/soft palate, maxilla, and mandible. It presents as a nodular lesion with a smooth or ulcerated surface. The initial treatment approach is chemotherapy, but this may vary according to the stage of lymphoma. The aim of this study was to report a case of NHL in the palate of a 54-year-old female patient, with extensive tissue destruction.

Complicações em coronectomia: estudo retrospectivo de 19 casos / Complications in coronectomy: retrospective study of 19 cases

Introdução: A Coronectomia ou Odontectomia parcial intencional é uma técnica cirúrgica, na qual se remove a coroa do dente, deixando a raiz in situ. É indicada quando há o risco de lesão ao nervo alveolar inferior ou fratura de mandíbula durante a remoção de dentes posteriores inferiores inclusos, particularmente os terceiros molares. Objetivo: Analisar as complicações trans e pós-operatórias e o índice de migração das raízes em 19 casos de coronectomia. Metodologia: Realizou-se um estudo retrospectivo através das informações contidas em prontuários e análise dos exames de imagem pré e pós-operatórios, com um período de acompanhamento que variou entre 6 meses e 4 anos e um mês de pós-operatório. Resultados: Foi observada uma queixa álgica e um caso de fragmento de esmalte dental residual. A migração radicular ocorreu em 89,5% dos casos e a movimentação média das raízes retidas foi de 3,21 milímetros, em um intervalo médio de 11 meses. Não foi necessária a reoperação de nenhum paciente. Conclusão: No presente estudo, a coronectomia mostrou-se ser uma boa opção à remoção completa do dente, com baixo índice de complicações... (AU)

Introduction: Coronectomy or Intentional Partial Odontoctomy is a surgical technique in which the crown is removed from the tooth that leaves the root in situ. It's indicated when there is a risk of injury to the inferior alveolar nerve or mandible fracture during the removal of included lower posterior teeth, particularly third molars. Objective: To analyze the trans and postoperative complications and the root migration index in 19 cases of coronectomy. Methodology: A retrospective study by the information contained in the medical records and analysis of the pre and post-operative imaging examinations was carried out, with a follow-up period ranging from 6 months to 4 years, and one month postoperatively. Results: Was observed a distress complaint and a case of residual dental enamel fragment were observed. The root migration occurred in 89.5% of the cases and the mean root movement was 3.21 millimeters, in an average interval of 11 months. No patient reoperation was required. Conclusion: In the present study coronectomy proved to be a good option for complete tooth removal, with a low rate of complications... (AU)

Post-mortem cytogenomic investigations in patients with congenital malformations.

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.

Cirurgia oral em paciente com anemia falciforme: o que o cirurgião-dentista precisa saber. Relato de caso / Oral surgery in patient with sickle cell disease: what the dentist need to know. Case report

Anemia falciforme é uma doença hereditária que se caracteriza por um distúrbio sanguíneo que afeta as células vermelhas, resultando, principalmente, em hemoglobinas alteradas. A doença caracteriza-se pela falta de glóbulos vermelhos saudáveis, causando dificuldade em transpor oxigênio para todos os tecidos. As manifestações sistêmicas e na cavidade oral podem ser variadas, sendo importante estar atento aos sinais clínicos e sintomas. Para o tratamento desses pacientes é necessário atenção aos cuidados e riscos a infecções oriundas das técnicas realizadas pelo cirurgião dentista, e, por esta razão, a antibioticoprofilaxia se faz tão necessária juntamente com a relação multidisciplinar. O objetivo deste trabalho foi apresentar um relato de caso de instalação de implante osseointegrado em paciente portadora de anemia falciforme, enfatizando as características da doença e os cuidados que o cirurgião-dentista deve ter no manejo destes pacientes.(AU)

Sickle cell disease is a hereditary disease characterized by a disorder that affects the blood red cells resulting mainly in altered hemoglobin. The disease results in lack of enough healthy red blood cells causing difficulty in transposing oxygen to all tissues. Systemic and bucal manifestations can be varied and it is very important to be aware of the clinical signs and symptoms. In the treatment of these patients it is necessary to pay attention for the risks of arising infections from the techniques performed by dentists and that´s why antibiotic prophylaxis is done as needed along with the multidisciplinary relationship. The objective of this study was a report of case of osseointegrated implant installation in a female patient with sickle cell anemia, emphasizing the characteristics of the disease and the care that the dentist must have in the management of these patients.(AU)

Cirurgia oral em pacientes hemofílicos: cuidados que o cirurgião-dentista precisa ter / Oral surgery in hemophilic patients: guidelines for the dental surgeon

A hemofilia é um distúrbio hemorrágico hereditário comum, caracterizada como uma desordem cromossômica ligado ao fator X, causando uma variedade de mutações no fator VIII (hemofilia A) e IV (hemofilia B). O objetivo do presente estudo foi, atráves de uma revisão da literatura, enfatizar os cuidados que o cirurgião-dentista deve ter na cirurgia oral com pacientes hemofílicos. Atualmente, quando se segue um protocolo, com fatores de reposição, antibiótico profilático, medidas hemostáticas locais e técnicas operatórias adequadas, o risco de hemorragia para pacientes hemofilícos, durante ou após cirurgias orais, diminui significativamente.

Hemophilia A is a common inherited bleeding disorder, characterized as a chromosome X-linked recessive bleeding factor, causing a variety of mutations in factors VIII (hemophilia A) and IV (hemophilia B). The aim of this study was, through a literature review, to emphasize the care with hemophilic patients in oral surgery. When an adequate protocol is followed, with spare factors, antibiotic prophylaxis, local hemostatic and appropriate surgical technique, the risk of hemorrhage for hemophilic patients during or after oral surgery signifi cantly decreases.

Tratamento cirúrgico de fístula bucossinusal de grande extensão: relato de caso / Surgical treatment of a large oroantral fistula: case report

Comunicação Bucossinusal é uma comunicação patológica que ocorre entre a cavidade oral e o seio maxilar. Quando esta comunicação sofre epitelialização passa a ser chamada de fistula bucossinusal. Surge principalmente após exodontia de dentes posteriores da maxila, devido à estreita relação de suas raízes com o assoalho do seio maxilar. Objetivo: Apresentar os tratamentos cirúrgicos utilizados para o fechamento de comunicação e fístula bucossinusal, bem como, descrever um relato de caso de uma fístula bucossinusal de grande extensão, esclarecendo a técnica utilizada passo a passo. Relato do caso: Paciente, do sexo feminino, 37 anos, apresentava fistula bucossinusal na região de molares superiores esquerdos e foi tratada cirurgicamente para fechamento da mesma. Sob anestesia local realizou-se uma incisão ao redor da fístula, cortando tecido epitelial a fim de permitir a união das bordas da ferida, sendo a região suturada por planos: inicialmente a mucosa do seio com fio catgut 4-0 e, em seguida, a gengiva, com fio de nylon, sem deixar margens cruentas. Os pontos foram removidos 10 dias após a cirurgia, observando-se, neste momento, o completo fechamento da fístula. Conclusão: Diversas técnicas cirúrgicas são utilizadas para o fechamento de fístulas bucossinusais e a sua escolha deve ser baseada no tamanho da comunicação, nas condições locais do tecido e habilidades do cirurgião. A técnica utilizada no presente caso mostrou-se efetiva e de fácil execução, proporcionando um pós-operatório confortável para o paciente e sem recidiva da comunicação...

Oroantral communication is a pathological communication that occurs between the oral cavity and the maxillary sinus. When this communication suffers epithelialization it is called oroantral fistula. It can occur mainly after extraction of posterior maxillary teeth, due to the close relationship between their roots and the maxillary sinus floor. Aim: To present the surgical options for the treatment of oroantral communication and report a case of a large oroantral fistula, explaining the technique step. Case Report: Female patient female, 37-year-old, presented bucossinusal fistula in the left upper molars area and was surgically treated for its closure. Under local anesthesia an incision was made around the fistula, cutting epithelial tissue to allow the union of the wound edges, and it was sutured by layers: initially sinus mucosa with 4-0 catgut and then the gums, with nylon. The suture was removed 10 days later and by this time the complete closure of the fistula was observed. Conclusion: The decision of which treatment modality to use for oroantral communication is influenced by many factors, such as its size, the tissue conditions and the surgeon’s skills. The surgical technique presented in this case proved effective and easy to perform, with a confortable postoperative period for the patient and with no recurrence of the communication...

Coronectomia em terceirosmolares inferiores: relato de dois casos / Coronectomy in inferior third molars: two cases case reports

A parestesia do nervo alveolar inferior, uma complicação decorrente de cirurgias de terceiros molares inferiores, é passível de acontecer principalmente quando sinais radiográficos indicam um íntimo contato das raízes com o canal da mandíbula. A tomografia computadorizada cone beam é o exame que confirma esse contato. Para estes casos, a coronectomia é uma opção cirúrgica, na qual é realizada a remoção apenas da porção coronária, com a manutenção das raízes localmente, minimizando, desta forma, o risco de parestesia. Objetivo: Apresentar o relato de dois casos clínicos de coronectomia no manejo de terceiros molares inferiores cuja radiografia panorâmica evidenciava íntima relação das raízes com o canal da mandíbula. Relato do caso: A técnica cirúrgica utilizada foi a mesma em ambos os casos. Sob anestesia local, realizou-se uma incisão tipo envelope, e o descolamento do retalho mucoperiostal. A osteotomia vestibular e distal foi realizada, expondo o dente ao nível da junção cemento-esmalte. Em seguida, iniciou-se a odontosecção, sendo realizada com uma extensão de 2/3 no sentido vestíbulo-lingual e 2 mm abaixo da junção cemento-esmalte; uma alavanca foi utilizada para separar a coroa das raízes. Realizou-se, por fim, o acabamento da superfície, deixando a superfície radicular 3 mm abaixo da crista óssea. Não houveram intercorrências trans ou pós-operatórias. Os pacientes permanecem sob acompanhamento radiográfico anual. Conclusão: A coronectomia é uma técnica eficaz, que reduz o risco de parestesia alveolar inferior, após a cirurgia de terceiros molares inferiores, cujas raízes estão próximas ao canal da mandíbula...

Oroantral communication is a pathological communication that occurs between the oral cavity and the maxillary sinus. When this communication suffers epithelialization it is called oroantral fistula. It can occur mainly after extraction of posterior maxillary teeth, due to the close relationship between their roots and the maxillary sinus floor. Aim: To present the surgical options for the treatment of oroantral communication and report a case of a large oroantral fistula, explaining the technique step. Case Report: Female patient female, 37-year-old, presented bucossinusal fistula in the left upper molars area and was surgically treated for its closure. Under local anesthesia an incision was made around the fistula, cutting epithelial tissue to allow the union of the wound edges, and it was sutured by layers: initially sinus mucosa with 4-0 catgut and then the gums, with nylon. The suture was removed 10 days later and by this time the complete closure of the fistula was observed. Conclusion: The decision of which treatment modality to use for oroantral communication is influenced by many factors, such as its size, the tissue conditions and the surgeon’s skills. The surgical technique presented in this case proved effective and easy to perform, with a confortable postoperative period for the patient and with no recurrence of the communication...

Transcriptional profile of fibroblasts obtained from the primary site, lymph node and bone marrow of breast cancer patients.

Cancer-associated fibroblasts (CAF) influence tumor development at primary as well as in metastatic sites, but there have been no direct comparisons of the transcriptional profiles of stromal cells from different tumor sites. In this study, we used customized cDNA microarrays to compare the gene expression profile of stromal cells from primary tumor (CAF, n = 4), lymph node metastasis (N+, n = 3) and bone marrow (BM, n = 4) obtained from breast cancer patients. Biological validation was done in another 16 samples by RT-qPCR. Differences between CAF vs N+, CAF vs BM and N+ vs BM were represented by 20, 235 and 245 genes, respectively (SAM test, FDR < 0.01). Functional analysis revealed that genes related to development and morphogenesis were overrepresented. In a biological validation set, NOTCH2 was confirmed to be more expressed in N+ (vs CAF) and ADCY2, HECTD1, HNMT, LOX, MACF1, SLC1A3 and USP16 more expressed in BM (vs CAF). Only small differences were observed in the transcriptional profiles of fibroblasts from the primary tumor and lymph node of breast cancer patients, whereas greater differences were observed between bone marrow stromal cells and the other two sites. These differences may reflect the activities of distinct differentiation programs.

Transcriptional effects of 1,25 dihydroxyvitamin D(3) physiological and supra-physiological concentrations in breast cancer organotypic culture.

BACKGROUND: Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)(2)D(3) (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)(2)D(3) in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)(2)D(3) at concentrations that can be attained in vivo. METHODS: Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)(2)D(3) 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)(2)D(3) 0.5nM, using RT-qPCR, western blot or immunocytochemistry. RESULTS: 1,25(OH)(2)D(3) 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)(2)D(3) near physiological concentration. Genes up-modulated by both 1,25(OH)(2)D(3) concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)(2)D(3) was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)(2)D(3) 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)(2)D(3) 0.5nM was detected. CONCLUSIONS: In breast cancer specimens a short period of 1,25(OH)(2)D(3) exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)(2)D(3) effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.

Differences in transcriptional effects of 1α,25 dihydroxyvitamin D3 on fibroblasts associated to breast carcinomas and from paired normal breast tissues.

The effects of 1α,25 dihydroxyvitamin D3 (1,25D) on breast carcinoma associated fibroblasts (CAFs) are still unknown. This study aimed to identify genes whose expression was altered after 1,25D treatment in CAFs and matched adjacent normal mammary associated fibroblasts (NAFs). CAFs and NAFs (from 5 patients) were cultured with or without (control) 1,25D 100 nM. Both CAF and NAF expressed vitamin D receptor (VDR) and 1,25D induction of the genomic pathway was detected through up-regulation of the target gene CYP24A1. Microarray analysis showed that despite presenting 50% of overlapping genes, CAFs and NAFs exhibited distinct transcriptional profiles after 1,25D treatment (FDR<0.05). Functional analysis revealed that in CAFs, genes associated with proliferation (NRG1, WNT5A, PDGFC) were down regulated and those involved in immune modulation (NFKBIA, TREM-1) were up regulated, consistent with anti tumor activities of 1,25D in breast cancer. In NAFs, a distinct subset of genes was induced by 1,25D, involved in anti apoptosis, detoxification, antibacterial defense system and protection against oxidative stress, which may limit carcinogenesis. Co-expression network and interactome analysis of genes commonly regulated by 1,25D in NAFs and CAFs revealed differences in their co-expression values, suggesting that 1,25D effects in NAFs are distinct from those triggered in CAFs.

Osteonecrose mandibular associada ao uso de bifosfonato: relato de caso / Biphosphonate related osteonecrosis of the jaw: case report

Introdução: os bifosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. Seu mecanismo de ação reduz a reabsorção óssea, a inibição do recrutamento e promoção da apoptose de osteoclastos. Apesar dos grandes benefícios para pacientes nestas condições, uma complicação associada ao seu uso é aosteonecrose dos maxilares. Objetivo: relatar um caso clínico envolvendo um paciente do sexo masculino de 72anos, sob tratamento endovenoso mensal com ácido zoledrônico, que evoluiu com osteonecrose espontânea bilateral em região posterior mandibular após um ano sob uso desta medicação. Conclusão: a conscientização dos Cirurgiões Dentistas quanto à etiologia da osteonecrosee a manutenção de ótima higiene oral nos pacientes sob uso destes medicamentos são fundamentais na prevenção da ocorrência desta condição.

Introduction: Biphosphonates are a group of drugs used to treat metástases associated with breast or prostate cancer and other bone diseases, including osteoporosis and Paget disease. They inhibit bone resorption through na action on osteoclasts slowing their activity and inducing apoptosis. Despite the benefits of biphosphonates, osteonecrosis of the jaw (ONJ) has emerged as a serious complication in some patients treated with these drugs. Aim: a case report of a 72-year-old male treated with zoledronic acid for one year that presented spontaneous bilateral ONJ is presented. Conclusion: the awareness of the dentists regarding the etiology of the ONJ and the maintenance of a great oral hygine by the patients under these medications are essencial for preventing this condition.

Terapia antitrombótica versus exodontia. Interromper ou não a medicação? / Antithrombotic therapy x tooth extraction. When to stop or not medication?

Terapias com agentes antiagregantes plaquetários e anticoagulantes têm sido utilizadas na prevenção e no tratamento de doenças tromboembólicas e cardiovasculares. Os medicamentos mais comumente utilizados são ácido acetilsalicílico, clopidogrel e varfarina. Cirurgias de exodontia em pacientes usuários de medicamentos antitrombóticos tornaram-se uma prática constante nos consultórios odontológicos. Tipicamente, era recomendado ao paciente alterar ou até mesmo suspender a medicação antes de procedimentos odontológicos onde houvesse risco de sangramento. Atualmente, as recomendações são para a não interrupção da medicação, uma vez que o risco de sangramento excessivo é baixo e medidas hemostáticas locais mostram-se eficientes.

Anticoagulant and antiplatelet agent therapies have been used in the prevention and treatment of thromboembolic and cardiovascular diseases. The most commonly used drugs used are aspirin, clopidogrel, and warfarin. Tooth extraction in patients undergoing these medications and presenting hemostatic abnormalities has become a constant practice in dental offices. Typically, it was recommended to change or even stop medication before dental procedures with risk of bleeding. However, current recommendations indicate that excessive bleeding is low and local hemostatic measures are effective.

Efeito da vitamina D no perfil transcricional de cultura organotípica de câncer de mama / Vitamin D effect in the transcriptional profile of breast cancer organotypic culture

1,25(OH)2D3 em concentrações elevadas (10-100nM) exerce efeito antiproliferativo e altera o perfil de expressão gênica de linhagens de câncer de mama. Entretanto, o estudo de linhagens não considera as interações epitéliomesênquima, as quais regulam o desenvolvimento do tumor. Além disso, elevadas concentrações de 1,25(OH)2D3 induzem hipercalcemia in vivo. Nossa proposta foi avaliar as ações de uma dose relativamente baixa de 1,25(OH)2D3, concentração que pode ser alcançada in vivo (0,5nM), e uma concentração farmacológica (100nM) em cultura organotípica de câncer de mama, modelo próximo ao fisiológico que simula as condições in vivo, no perfil de expressão gênica.Para isto, avaliamos a integridade da via pela indução do gene alvo CYP24A1. Inicialmente foram avaliadas amostras de 5 pacientes. Biópsias de câncer de mama foram seccionadas, cultivadas e tratadas por 24h com 1,25(OH)2D3 0.5nM ou 100nM. A cultura organotípica manteve-se viável com preservação das características teciduais e índice de proliferação. O perfil de expressão gênica foi determinado pela análise do chip de microarray (U133 Plus 2.0, Affymetrix). Foram regulados 394 genes (Repeated Measures ANOVA, p<0.05, variação de expressão ³ 1,5) incluindo genes envolvidos em resposta imune e metabolismo celular primário. Foram selecionados 7 genes vitamina D induzidos (cuja variação de expressão foi ³ 2 e concordância no sentido da regulação). Análises complementares foram realizadas em um segundo grupo de pacientes (n=16) cujas amostras foram processadas da mesma maneira por qPCR. Estes genes eram: CD14, IL33, BMP6; DPP4, CA2, SHE e IL1RL1. Observou-se indução da expressão de CA2, DPP4 e CD14 mediante tratamento com 1,25(OH)2D3 100nM e CA2, também pela concentração 0,5nM. Além disso, avaliamos a expressão de genes candidatos num modelo in vitro de transformação mamária composto por células HME, HMELT, HMELT+Ras e também a linhagem MCF7, sob as mesmas condições de tratamento (por qPCR, western blotting microscopia confocal e Elisa)...

High 1,25(OH)2D3 (VD) concentrations (10-100nM) exerts antiproliferative effects and modifies gene expression profile in breast cancer (BC) cell lines. However, studies conducted in cell lines disconsider stromal-epithelium interactions, which are known to regulate breast cancer development. Besides, high VD concentrations may cause hypercalcemia in vivo. Our aim was to evaluate the effects of a relatively low (0,5nM) concentrations of 1,25(OH)2D3 which can be attained in vivo, and pharmacological concentrations (100nM) in an organ culture model, a physiological model which mimics in vivo conditions, by means of differential gene expression profile. Vitamin D pathway integrity was evaluated by the expression of the target gene, CYP24A1. Freshly excised human BC tumor samples were sliced and cultivated in complete culture media containing vehicle, 0.5nM or 100nM 1,25(OH)2D3 for 24 hours. Organotypic culture remained viable with preserved tissue architecture and proliferation index for at least 24 hours. Affymetrix (U133 Plus 2.0) gene expression profiles obtained in five separate tissue samples for each treatment revealed 394 regulated genes (Repeated Measures ANOVA, p<0.05, fold induction ³ 1,5). Biological functions over-represented included immune response and primary cellular metabolism. Expression of seven candidate genes (CD14, IL33, BMP6; DPP4, CA2, SHE and IL1RL1; fold induction ³ 2) was further evaluated in a large number of samples (n=16) using qPCR. Among them, CA2, DPP4 and CD14 were induced by 1,25(OH)2D3 100nM. CA2 was also induced after 1,25(OH)2D3 0.5nM treatment. Expression of candidate genes was also assessed in a model of mammary epithelial cell transformation HME, HMELT, HMELT+Ras and also MCF7 cells treated with VD by qPCR, western blotting, confocal microscopy and ELISA assays. The seven genes were confirmed upregulated by VD (RT-qPCR analysis) in the cell transformation model. Among them, CD14, IL1RL1 and SHE were also modulated in...

Expressão de caderinas e fator repressor em tumor de pacientes com câncer de mama na presença ou ausência de células malignas em medula óssea / Cadherins and repressor tumor factor expression in breast cancer patients in the presence or absence of malignant cells in bone marrow

OBJETIVO: Acredita-se que o perfi l gênico do tumor é diferente daquele do tecido normal. Além disso, é possível que o tumor adquira características que lhe conferem potencial de gerar metástases em sítios específi cos. A expressão tumoral de Caderinas 3 e 11 (envolvidas em adesão e migração celular), e de CBX3 (repressor transcricional) pode estar relacionada amaior agressividade e potencial invasivo em pacientes com câncer de mama (CM). Nosso objetivo é comparar a expressão de Caderina 3, Caderina 11 e CBX3 em tumor e tecido mamário normal adjacente e correlacionar a expressão tumoral destes genes com colonização da medula óssea (MO) por células tumorais...

PURPOSE: Gene profi le is believed to be different in tumor and normal tissue.Besides, it is possible that tumor acquires characteristics that provide ability to develop metastasisin specifi c sites. Tumoral expression of Cadherins 3 and 11 (involved with adhesion and cellular migration) and CBX3 (transcriptional repressor) may be related to aggressiveness andlower survival in breast cancer (BC) patients. Our purpose is to compare tumoral and normal mammary tissue expression of Cadherin 3, Cadherin 11 and CBX3 and to correlate tumoralexpression of these genes with bone marrow (BM) colonization by tumoral cells...