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Cutaneous lesions are one of the hallmarks of tuberous sclerosis complex (TSC), a genetic disease in which mTOR is hyperactivated due to the lack of hamartin or tuberin. To date, novel pharmacological treatments for TSC cutaneous lesions that are benign but still have an impact on a patient's life are needed, because neither surgery nor rapamycin administration prevents their recurrence. Here, we demonstrated that primary TSC2

Senescence is a stress-response process characterized by the irreversible inhibition of cell proliferation, associated to the acquisition of a senescence-associated secretory phenotype (SASP), that may drive pathological conditions. Lymphangioleiomyomatosis (LAM) is a rare disease in which LAM cells, featuring the hyperactivation of the mammalian Target of Rapamycin Complex 1 (mTORC1) for the absence of tuberin expression, cause the disruption of the lung parenchyma. Considering that LAM cells secrete SASP factors and that mTOR is also a driver of senescence, we deepened the contribution of senescence in LAM cell phenotype. We firstly demonstrated that human primary tuberin-deficient LAM cells (LAM/TSC cells) have senescent features depending on mTOR hyperactivation, since their high positivity to SA-β galactosidase and to phospho-histone H2A.X are reduced by inducing tuberin expression and by inhibiting mTOR with rapamycin. Then, we demonstrated the capability of LAM/TSC cells to induce senescence. Indeed, primary lung fibroblasts (PLFs) grown in LAM/TSC conditioned medium increased the positivity to SA-β galactosidase and to phospho-histone H2A.X, as well as p21WAF1/CIP1 expression, and enhanced the mRNA expression and the secretion of the SASP component IL-8. Taken together, these data make senescence a novel field of study to understand LAM development and progression.

Matrix metalloproteinase (MMP) dysregulation is implicated in several diseases, given their involvement in extracellular matrix degradation and cell motility. In lymphangioleiomyomatosis (LAM), a pulmonary rare disease, MMP-2 and MMP-9 have been detected at high levels in serum and urine. LAM cells, characterized by a mutation in the tuberous sclerosis complex (TSC)1 or TSC2, promote cystic lung destruction. The role of MMPs in invasive and destructive LAM cell capability has not yet been fully understood. We evaluated MMP-2 and MMP-7 expression, secretion, and activity in primary LAM/TSC cells that bear a TSC2 germline mutation and an epigenetic modification and depend on epidermal growth factor (EGF) for survival. 5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody. Both drugs reduced MMP-2 and MMP-7 secretion and activity during wound healing and decreased their expression in lung nodules of a LAM mouse model. In LAM/TSC cells, MMP-2 and MMP-7 are dependent on tuberin expression, cellular adhesion, and migration. MMPs appears sensitive to rapamycin and anti-EGFR antibody only during cellular migration. Our data indicate a complex and differential modulation of MMP-2 and MMP-7 in LAM/TSC cells, likely critical for lung parenchyma remodeling during LAM progression.

Background: Lymphangioleiomyomatosis can develop in a sporadic form (S-LAM) or in women with tuberous sclerosis complex (TSC). The matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes potentially involved in cystic lung destruction, and in the process of migration of LAM cells. The aim of the study was to explore the role of MMP-2 and MMP-7, such as vascular endothelial growth factor (VEGF) -C and -D in women with LAM, including patients with minor pulmonary disease (i.e.

Multiple myeloma is still incurable due to an intrinsic aggressiveness or, more frequently, to the interactions of malignant plasma cells with the bone marrow (BM) microenvironment. Myeloma cells educate BM cells to support neoplastic cell growth, survival, acquisition of drug resistance resulting in disease relapse. Myeloma microenvironment is characterized by Notch signaling hyperactivation due to the increased expression of Notch1 and 2 and the ligands Jagged1 and 2 in tumor cells. Notch activation influences myeloma cell biology and promotes the reprogramming of BM stromal cells. In this work we demonstrate, in vitro, ex vivo and by using a zebrafish multiple myeloma model, that Jagged inhibition causes a decrease in both myeloma-intrinsic and stromal cell-induced resistance to currently used drugs, i.e. bortezomib, lenalidomide and melphalan. The molecular mechanism of drug resistance involves the chemokine system CXCR4/SDF1α. Myeloma cell-derived Jagged ligands trigger Notch activity in BM stromal cells. These, in turn, secrete higher levels of SDF1α in the BM microenvironment increasing CXCR4 activation in myeloma cells, which is further potentiated by the concomitant increased expression of this receptor induced by Notch activation. Consistently with the augmented pharmacological resistance, SDF1α boosts the expression of BCL2, Survivin and ABCC1. These results indicate that a Jagged-tailored approach may contribute to disrupting the pharmacological resistance due to intrinsic myeloma cell features or to the pathological interplay with BM stromal cells and, conceivably, improve patients' response to standard-of-care therapies.

Tuberous Sclerosis Complex (TSC) is characterized by the presence of benign tumors in the brain, kidneys, heart, eyes, lungs, and skin. The typical brain lesions are cortical tubers, subependimal nodules and subependymal giant-cell astrocytomas. The occurrence of malignant astrocytomas such as glioblastoma is rare. We report on a child with a clinical diagnosis of TSC and a rapidly evolving glioblastoma multiforme. Genetic analysis identified a de novo mutation in TSC2. Molecular characterization of the tumor was performed and discussed, as well as a review of the literature where cases of TSC and glioblastoma multiforme are described. Although the co-occurrence of TSC and glioblastoma multiforme seems to be rare, this possible association should be kept in mind, and proper clinical and radiological follow up should be recommended in these patients.

Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells, Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The effects of rosuvastatin on the function of human TSC2 −/− and TSC2 -/meth α -actin smooth muscle (ASM) cells have been investigated. The TSC2 −/− and TSC2 -/meth ASM cells, previously isolated in our laboratory from the renal angiomyolipoma of two TSC patients, do not express tuberin and bear loss of heterozigosity caused by a double hit on TSC2 and methylation of TSC2 promoter, respectively. Exposure to rosuvastatin affected TSC2 -/meth ASM cell growth and promoted tuberin expression by acting as a demethylating agent. This occurred without changes in interleukin release. Rosuvastatin also reduced RhoA activation in TSC2 -/meth ASM cells, and it required coadministration with the specific mTOR (mammalian target of rapamycin) inhibitor rapamycin to be effective in TSC2 −/− ASM cells. Rapamycin enhanced rosuvastatin effect in inhibiting cell proliferation in TSC2 −/− and TSC2 -/meth ASM cells. Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal-regulated kinase (ERK), and at the higher concentration, rosuvastatin and rapamycin slightly decreased ERK phosphorylation. These results suggest that rosuvastatin may potentially represent a treatment adjunct to the therapy with mTOR inhibitors now in clinical development for TSC. In particular, rosuvastatin appears useful when the disease is originated by epigenetic defects.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects.

Lymphangioleiomyomatosis (LAM) is an interstitial lung disease characterized by invasion and proliferation of abnormal smooth muscle (ASM) cells in lung parenchyma and axial lymphatics. LAM cells bear mutations in tuberous sclerosis ( TSC ) genes. TSC2 −/− ASM cells, derived from a human renal angiomyolipoma, require epidermal growth factor (EGF) for proliferation. Blockade of EGF receptors (EGFR) causes cell death. TSC2 −/− ASM cells, previously labeled with PKH26-GL dye, were endonasally administered to 5-week-old immunodeficient female nude mice, and 4 or 26 weeks later anti-EGFR antibody or rapamycin was administered twice a week for 4 consecutive weeks. TSC2 −/− ASM cells infiltrated lymph nodes and alveolar lung walls, causing progressive destruction of parenchyma. Parenchymal destruction was efficiently reversed by anti-EGFR treatment and partially by rapamycin treatment. Following TSC2 −/− ASM cell administration, lymphangiogenesis increased in lungs as indicated by more diffuse LYVE1 expression and high murine VEGF levels. Anti-EGFR antibody and rapamycin blocked the increase in lymphatic vessels. This study shows that TSC2 −/− ASM cells can migrate and invade lungs and lymph nodes, and anti-EGFR antibody is more effective than rapamycin in promoting lung repair and reducing lymphangiogenesis. The development of a model to study metastasis by TSC cells will also help to explain how they invade different tissues and metastasize to the lung.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that is caused by mutations in either the TSC1 or TSC2 gene. Smooth muscle-like cells (ASMs) were isolated from an angiomyolipoma of a patient with TSC. These cells lacked tuberin, were labeled by both HMB45 and CD44v6 antibodies, and had constitutive S6 phosphorylation. The cells bear a germline TSC2 intron 8-exon 9 junction mutation, but DNA analysis and polymerase chain reaction amplification failed to demonstrate loss of heterozygosity. Testing for an epigenetic alteration, we detected methylation of the TSC2 promoter. Its biological relevance was confirmed by tuberin expression and a reduction in HMB45 labeling and S6 constitutive phosphorylation after exposure to the chromatin-remodeling agents, trichostatin A and 5-azacytidine. These cells were named TSC2(-/meth) ASMs. Their proliferation required epidermal growth factor in the medium as previously described for TSC2(-/-) ASMs. Blockade of epidermal growth factor with monoclonal antibodies caused the death of TSC2(-/meth) ASMs. In addition, rapamycin effectively blocked the proliferation of these cells. Our data show for the first time that methylation of the TSC2 promoter might cause a complete loss of tuberin in TSC2 cells, and that the pathogenesis of angiomyolipomas might also originate from epigenetic defects in smooth muscle cells. Additionally, the effect of chromatin-remodeling agents in these cells suggests a further avenue for the treatment of TSC as well as lymphangioleiomyomatosis.

Tuberous Sclerosis Complex (TSC) is characterized by the presence of benign tumors in the brain, kidneys, heart, eyes, lungs, and skin. The typical brain lesions are cortical tubers, subependimal nodules and subependymal giant-cell astrocytomas. The occurrence of malignant astrocytomas such as glioblastoma is rare. We report on a child with a clinical diagnosis of TSC and a rapidly evolving glioblastoma multiforme. Genetic analysis identified a de novo mutation in TSC2. Molecular characterization of the tumor was performed and discussed, as well as a review of the literature where cases of TSC and glioblastoma multiforme are described. Although the co-occurrence of TSC and glioblastoma multiforme seems to be rare, this possible association should be kept in mind, and proper clinical and radiological follow up should be recommended in these patients.

EGFR belongs to the HER/ErbB family of tyrosine kinase receptors and its activation in cancer cells has been linked with increased proliferation, angiogenesis, and metastasis. Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that occurs sporadically or in association with tuberous sclerosis complex (TSC), a genetic, multisystem disorder characterized by hamartomas in several organs. From chylous of a LAM/TSC patient, we previously isolated smooth muscle-like LAM/TSC cells whose proliferation depends on EGF and monoclonal anti-EGFR antibodies reduced proliferation and caused cell death. We demonstrated that the dependency from EGF was caused by the absence of tuberin. To study the role of EGFR pathwayin vivo, we developed a mouse model by administration of LAM/TSC cells to female nude mice. LAM/TSC cells caused pulmonary airspace enlargement and, after 30 weeks, nodule formation which express EGFR. Anti-EGFR antibody decreased the number and dimension of lung nodules likely for the inhibition of Erk and S6 signaling, reversed the pulmonary alterations, and reduced lymphatic and blood vessels. Moreover, in pulmonary nodules anti-EGFR antibody reduced the positivity to estrogen and progesterone receptors which enhance survival of LAM cells and Snail expression. These results suggest that the inhibition of EGFR signalling has a potential in treatment of LAM/TSC lung alterations.

International audience; Floating Car Data (FCD) consist of information generated by moving vehicles and uploaded to Internet-based control centers for processing and analysis. As upcoming mobile services based on or built for networked vehicles largely rely on uplink transfers of small-sized but high-frequency messages, FCD traffic is expected to become increasingly common in the next few years. Presently, FCD are managed through a traditional cellular network paradigm : however, the scalability of such a model is unclear in the face of massive FCD upload, involving large fractions of the vehicles over short time intervals. In this paper, we explore the use of vehicle-to-vehicle (V2V) communication to partially relieve the cellular infrastructure from FCD traffic. Specifically, we study the performance boundaries of such a FCD offloading approach in presence of best- and worst-case data aggregation possibilities at vehicles. We show the gain that can be obtained by offloading FCD via vehicular communication, and propose a simple distributed heuristic that has nearly optimal performance under any FCD aggregation model.

Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting almost exclusively women, characterized by the invasion and abnormal proliferation of smooth muscle-like cells in pulmonary parenchyma and axial lymphatics. LAM cells bear mutations in Tuberous Sclerosis Complex (TSC) genes. It has been hypothesized that uterus might be the primary site of origin and one of the most frequent metastatic or disseminated site of LAM cells. We developed a mouse model to study the migratory and invasive properties of human LAM/TSC cells to the uterus. We also examined the action of rapamycin and anti-Epidermal Growth Factor Receptor (EGFR) antibody. LAM/TSC cells were endonasally administered to 3 week old immunodeficient female nude mice. 5 months later mice were divided in 4 groups: control, LAM/TSC cell-administered mice, LAM/TSC cell-administered mice treated with rapamycin, and LAM/TSC cell-administered mice treated with anti-EGFR antibody. Drugs were administered for one months. Uteri were analysed for the presence of human LAM/TSC cells by COX IV antibody, lymphangiogenesis by LYVE 1 expression and angiogenesis by counting blood vessels. LAM/TSC cells migrated to the uterus without causing any morphological lesion. Interestingly, LAM/TSC cells increased the number of blood vessels while did not cause any alteration in lymphatics vessels. Anti-EGFR antibody and rapamycin reduced the number of human LAM/TSC and counteracted the proliferation of blood vessels in uteri. Although both drugs did not change the expression of LYVE 1, localization of lymphatics was mainly in the perimetrium after drug treatment. Our data describe the strong invasive capability of human LAM/TSC cells which migrated to the uterus. LAM/ TSC cells presence is accompanied by increased angiogenesis. Anti-EGFR antibody and rapamycin were effective in reducing the LAM/TSC cell number and blood vessel proliferation.

Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 or TSC2 genes. Lymphangioleiomyomatosis (LAM) can be sporadic or associated with TSC and is characterized by widespread pulmonary proliferation of abnormal α-smooth muscle (ASM)-like cells. We investigated the features of ASM cells isolated from chylous thorax of a patient affected by LAM associated with TSC, named LAM/TSC cells, bearing a germline TSC2 mutation and an epigenetic defect causing the absence of tuberin. Proliferation of LAM/TSC cells is epidermal growth factor (EGF)-dependent and blockade of EGF receptor causes cell death as we previously showed in cells lacking tuberin. LAM/TSC cells spontaneously detach probably for the inactivation of the focal adhesion kinase (FAK)/Akt/mTOR pathway and display the ability to survive independently from adhesion. Non-adherent LAM/TSC cells show an extremely low proliferation rate consistent with tumour stem-cell characteristics. Moreover, LAM/TSC cells bear characteristics of stemness and secrete high amount of interleukin (IL)-6 and IL-8. Anti-EGF receptor antibodies and rapamycin affect proliferation and viability of non-adherent cells. In conclusion, the understanding of LAM/TSC cell features is important in the assessment of cell invasiveness in LAM and TSC and should provide a useful model to test therapeutic approaches aimed at controlling their migratory ability.

BACKGROUND: Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2(-/-) ASM cell proliferation is EGF-dependent. METHODS AND FINDINGS: Effects of EGF on proliferation of TSC2(-/-) ASM cells and TSC2(-/-) ASM cells transfected with TSC2 gene were determined. In contrast to TSC2(-/-) ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2(-/-) ASM cells. Exposure of TSC2(-/-) ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2(-/-) cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2(-/-) ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2(-/-) ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. CONCLUSION: Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC(-/-) ASM cells, and such EGF-dependency is the result of the lack of tuberin.

The biochemical and cytochemical effects of cytosine arabinoside (Ara C) and of hydrocortisone on HeLa cells in vitro have been studied. In cultures treated with Ara C, a relationship exists between the cytocidal effects of the drug and an increase in alkaline phosphatase. Although hydrocortisone had no influence on the proliferative rhythm, it induced an increase in alkaline phosphatase. Results obtained with the cytochemical technique were evaluated, particularly in relation to enzyme localization.

Injections of homologous skin suspensions in Freund's adjuvant appreciably increased the carcinogenic effect of methylcholanthrene. Four months after the first painting with methylcholanthrene, cancer was present in 11 of 16 mice injected with skin suspension, whereas only 4 of the 18 non injected mice had cancer. Serological tests demonstrated the presence of antiskin antibodies in the injected animals. The results seem to indicate that immunological mechanisms may be involved in skin carcinogenesis.

A supervisão em Psicologia nas universidades é um espaço privilegiado de aprendizagem, ancorado principalmente na relação que se estabelece entre estagiário e o professor-supervisor. Esta pesquisa apresenta um estudo que enfoca a prática de supervisão em universidades do Brasil, Portugal e Uruguai, a fim de identificar e descrever o percurso realizado pelos participantes para se tornarem supervisores de psicologia clínica nas universidades pesquisadas, analisar os pré-requisitos necessários para ser um supervisor, discutir a importância da vivência prática para garantir a qualidade da supervisão traçando aproximações e diferenças nos diferentes países. Foram entrevistados 13 professores supervisores de estágio em psicologia clínica de duas universidades de Portugal, uma do Uruguai e três do Brasil. Foram escolhidos Portugal e Uruguai, o primeiro por ser submetido a declaração de Bologna, documento que legisla sobre o ensino superior na Europa, e o segundo por ser membro, junto com o Brasil, do Mercosul, que apresenta diretrizes comuns para o curso de Psicologia nos países da América do Sul. O método proposto é o qualitativo, por meio de questionário e entrevista semiestruturada elaborados pelo pesquisador com supervisores das diferentes universidades. Para análise e discussão utilizou-se análise de conteúdo. Os resultados apontam que tornar-se supervisor é um processo natural que se inicia com a docência teórica em sala de aula nos três países estudados, embora todos os participantes considerem a presença de pré-requisitos específicos para ser um supervisor de estágio, já que a supervisão é um espaço que convoca uma posição de maior proximidade entre supervisor e supervisionando. A pesquisa pode trazer contribuições para um estudo mais aprofundado dos instrumentos de ensino-aprendizagem em psicologia nas universidades, a partir de critérios mais objetivos e sistematizados de enquadre, manejo e didática da supervisão. Uma formação específica para se tornar um supervisor clínico foi considerada uma estratégia positiva Supervision in Psychology at universities is a privileged learning space, anchored mainly in the relationship established between internship and supervisor. This research presents a transnational study that focuses on the practice of supervision in universities in Brazil, Portugal and Uruguay. Its purpose is to identify and describe the course taken by the participants to become supervisors of clinical psychology in the researched universities, to analyze the necessary requirements to be a supervisor and to discuss the importance of practical experience to guarantee the quality of supervision, drawing approximations and differences among the countries involved in the study. Thirteen (13) intern supervisors were interviewed with emphasis on clinical psychology from two universities in Portugal, one from Uruguay and three from Brazil. Portugal was chosen because it is submitted to the Bologna Declaration, a document that legislates on higher education in Europe, while Uruguay was chosen because it is a member of Mercosur along with Brazil, which presents common guidelines for Psychology courses in countries of South America. Qualitative method was chosen, which was done through a questionnaire and semi-structured interview elaborated by the researcher with supervisors of different universities. A content analysis was used as a method for analysis and discussion. The results show that becoming a supervisor is a natural process that starts with theoretical teaching in the classroom in these three relevant countries, although all participants consider the presence of specific requirement to be an intern supervisor, since supervision is a space that calls for a more close interaction between supervisor and supervised. The research can contribute to a more in-depth study of teaching-learning instruments in psychology in universities based on objective and systematized framework criteria, management and supervision didactics. Specific training to become a clinical supervisor was considered as a positive strategy

A presente tese tem por finalidade propor algumas idéias que possam sustentar o que denominamos \"Pedagogia de Desconstrução\", idéias estas desdobradas com base na ontologia fundamental de Martin Heidegger, publicada em 1927 (Ser e tempo) e das publicações realizadas a partir de 1930, que marcaram a virada (die Kehre) do seu pensamento. O sentido da palavra desconstrução (Ab-Bau) ou destruição (Detruktion) em Heidegger está associado à identificação de um modo de pensar característico do ocidente, denominado pensamento metafísico, que se estabeleceu a partir de Platão. Tal modo de pensar consolida-se por meio de uma interpretação objetivada do ser dos entes (Vorhandenheit), cujos desdobramentos fizeram com que a metafísica esquecesse o fenômeno do mundo, permanecendo presa ao modelo do ver teorético. O sentido da desconstrução alinha-se com a tentativa de recuperar a diferença ontológica entre ser e ente, portanto, desconstruir o modo objetivado de alocar o ser dos entes, meditar sobre o sentido do ser e re-visitar (An-denken) o pensamento metafísico, desvelando aquilo que não foi pensado pela educação a partir destas determinações metafísicas. O modo de pensar metafísico chega à plenitude de suas possibilidades em nossa época atual, séculos 20 e 21, exercida por dois fenômenos que são: a ciência e a técnica moderna, que vem impor um modo de ser e pensar sobre cujas conseqüências Heidegger procurou nos alertar quanto às suas conseqüências nas significativas conferências realizadas após 1930. Tal modo de pensar, instrumentado pela eficiência da técnica e da logística dos mercados, nos enreda numa pseudoproximidade com as coisas e com os outros, entre outros sintomas que nos fazem adentrar numa noite escura e densa, obscurecendo-nos o mundo. Podemos testemunhar este mundo obscurecido por meio de alguns sintomas de nossa época atual, como a massificação dos homens, da fuga dos deuses, a devastação da terra, a aniquilação da coisa, bem como pela técnica moderna cuja essência consolida-se como uma contenda, uma provocação do homem em relação à natureza. É diante destes alertas demonstrados por Heidegger e testemunhados por nós que pensamos em propor algumas idéias que possam orientar uma pedagogia, preocupada em exercer alguns contrapontos aos imperativos de nossa época atual. Conscientes dos limites deste projeto em consonância com os entendimentos de Heidegger sobre os limites de nosso empenho em relação à metafísica, estamos propondo algumas pequenas saídas que se consolidam na tentativa de resgatar o vigor de um pensar que se realiza na unidade entre ser e pensar, de \"conduzir\" (ex-ducere) o ser-aí em direção ao conhecimento de si mesmo e de voltar-se para uma relação com o real pautada pela poiésis, ou seja, por uma linguagem e por um fazer que envolve levar à luz o que se apresenta realizado pela essência da verdade, compreendida como sendo a liberdade de deixar ser o ente. É neste âmbito da poiésis que o pensamento e os afazeres dos homens podem desconstruir o modo de desvelar o ser dos entes, dominado por um pensamento cuja armação (Gestell) submete as coisas à tríade: exploração, produção e consumo. O âmbito da poiésis em Heidegger inspira-se no poeta Hölderlin e com ele gesta-se a possibilidade de um outro modo de relação com o real, cujos modelos ônticos exercem um contraponto à armação, modelos estes inscritos no que Heidegger denomina por quadrindade, constituída pelo espelhamento entre os diferentes envios do ser: a terra; e o céu; os divinos e os mortais. The aim of this thesis is to propose some ideas supporting what we refer to as \"Deconstruction Teaching\", arising from Martin Heidegger\'s 1927 work on basic ontology (Being and Time) and other publications as of 1930, marking the turning point (die Kehre) in his thinking. For Heidegger, the meaning of the term deconstruction (Ab-Bau) or destruction (Detruktion) is associated with a characteristic Western manner of thinking, known as metaphysical thinking, a concept originally identified by Plato. This manner of thinking is reinforced through the objective interpretation of the being of being (Vorhandenheit), an approach whereby metaphysics ignores the world phenomenon, and remaines mired in the theoretical view model. The meaning of deconstruction becomes aligned with the attempt to recover the ontological difference between being and the being and, thus, deconstructs the objective interpretation of allocating the being of the beings, to meditate on the meaning of the being and revisiting (An-denken) metaphysical thought, in order to reveal that which was not considered by education based on these metaphysical conclusions. The manner of metaphysical thinking reached the peak of its capacity in our own times, the twentieth and twenty-first centuries. It was exercised by two phenomena, science and modern techniques, which themselves imposed a way of being and of thinking of whose consequences Heidegger strove to warn us in key talks given after 1930. This way of thinking, led by the efficient techniques and logistics of the markets, binds us into pseudo-proximity with things and with others, among other symptoms that thrust us into a dark and dense night, blinding us to the world. We can witness this obscured world through some of the symptoms of our time. Examples are the reduction of humans to their lowest common denominator, the exodus of the gods, the devastation of the earth, the annihilation of the thing, in addition to modern techniques, whose essence has hardened into dispute, man provoking nature. It is thanks to Heidegger\'s warnings which we ourselves have also witnessed, that we decided to present some ideas that could steer teaching, in its anxiety to place some counterpoints to today\'s imperatives. We are aware of the limits of this project in accordance with Heidegger\'s views on the limits of our performance in relation to metaphysics, and propose some minor solutions that arose in the attempt to redeem the vigor of a thinking process developed in the space between to be and to think, of \"leading forth\" (ex-ducere) being in the direction of self-knowledge and to return to a relationship with what is real, based on poiesis. In other words, through a language and through action involving bringing to light what is realized by the essence of truth, understood as being the freedom to cease being the being. It is in this very environment of poiesis that man\'s thoughts and actions can deconstruct the manner of revealing the being of the beings, dominated by a thought whose configuration (Gestell) submits such things to that trinity of exploration, production, and consumption. The environment of poesis in Heidegger was inspired by the poet Hölderlin and it is with him that the possibility of another relationship with reality is born, one whose ontological models exercise a counterpoint to this configuration. These models are part of what Heidegger defines as the \"quadrinity\", formed by the reflection of three different aspects of the being: earth, heaven, the gods, and mortals.