O objetivo deste estudo foi comparar em 6 meses os resultados do recobrimento radicular, hipersensibilidade dentinária, dor pós-operatória e estética utilizando o retalho avançado coronalmente modificado (RACm) associado ao enxerto de tecido conjuntivo subepitelial (ETCS) ou a matriz de colágeno suíno (MC) no tratamento de retrações gengivais (RG). Neste ensaio clínico aleatório cego de não-inferioridade, desenho de boca dividida, quinze pacientes com RG superiores múltiplas adjacentes, classe I de Miller, localizadas em caninos e pré-molares, com pelo menos uma RG >= 3 mm foram selecionados e distribuídos aleatoriamente em grupo controle (RACm+ETCS) e grupo de teste (RACm+MC). A altura da RG residual (desfecho primário) foi menor para o grupo controle (0,3 ± 0,6 mm) comparado ao grupo teste (0,6 ± 1,0 mm) (p = 0,008). A porcentagem de recobrimento radicular foi de 89,3% para o grupo controle e 77,7% para o grupo teste. Ambos os grupos demonstraram ganho em largura do TQ em 6 meses (p < 0,05) com diferença entre os grupos (p = 0,031). A profundidade de sondagem e o ganho de nível clínico de inserção foram similares entre os grupos e em todos os períodos avaliados. Ambos os grupos foram eficazes na redução da hipersensibilidade dentinária. A dor pósoperatória foi maior no grupo controle comparada ao grupo teste. A satisfação estética do paciente e do periodontista foi alta independente do grupo sem diferença estatística e a formação de cicatriz nas papilas e as diferenças visuais nas áreas enxertadas foram maiores no RACm+ETCS. Quando equilibrados os resultados clínicos de cobertura radicular, os resultados centrados no paciente e a satisfação estética, a associação RACm+MC é uma alternativa viável ao RACm+ETCS para o tratamento das RG múltiplas. / The aim of this study was to compare the 6 months outcome of root coverage, dentin hypersensitive, pain after surgery and aesthetics using the modified coronal advanced flap (mCAF) associate with connective tissue graft (CTG) or collagen matrix (CM) in the treatment of gingival recession (GR). Fifteen patients with superior multiple recessions in canines and pre-molars were selected for this non-inferority randomized clinical trial, which was divided in control group (mCAF+CTG) and test group (mCAF+CM). The residual GR (primary outcome) was lower for control group (0,3 ± 0,6 mm) comparing with test group (0,6 ± 1,0 mm) (p = 0,008). The root coverage percentage was 89,3% for control group and 77,7% for test group. Both groups demonstrated gain of keratinized tissue in 6 months (p < 0,05) statically different between groups (p = 0,031). The probing depth and gain of clinical attachment level were similar between the groups in all evaluated periods. Dentin hypersensitive was reduced in all groups. The pain after surgery was higher in control group comparing with test group. Aesthetic satisfaction evaluated by patient and periodontist was high independently of group with no statistical difference, however, the scar formation at papillae base and visual differences were visually higher using mCAF+CTG. Considering the clinical outcomes balanced with patient related outcomes and aesthetic satisfaction, the use of mCAF+CM is a alternative to mCAF+CTG in the treatment of multiple gingival recession.

<p>In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored.</p><p>It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed.</p><p>In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.</p>

In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored. It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed. In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.

Orientador: Carlos Alberto Anaruma / Banca: Roberto Naves Domingos / Banca: Miriam Maria de Magalhães Oliveira / Resumo: Este trabalho apresenta uma série de resultados referentes à utilização da transmissão de fármacos tópicos através de ondas ultra-sônicas (fonoforese), em lesão cirúrgica produzida no músculo tibial anterior de ratos Wisttar. O fármaco utilizado foi a hidrocortisona gel manipulada a 10%. Foram utilizados 42 ratos Wisttar machos, com 60 dias de idade e peso médio de 300,0 g ( 50,0 g), que foram submetidos à lesão cirúrgica na pata direita no músculo tibial anterior. Após 24 horas a área da lesão foi tratada com ultra-som tendo como gel acoplante hidrocortisona a 10%. A freqüência utilizada foi de 1,0 MHz e intensidade de 0,4 W/cm2 por 1 minuto, durante 14 dias consecutivos. Depois da terapia aplicada os ratos foram sacrificados, o músculo criofixado e cortado em criostato. As lâminas obtidas foram coradas por H/E, Tricrômico de Masson e Tricrômico de Mallory para serem fotografadas em fotomicroscópio Zeiss. O tecido analisado proveniente dos animais lesados, tratados com ultra-som e hidrocortisona a 10% (fonoforese) apresentam: após 1 dia de tratamento, fibras musculares seccionadas pela incisão já fagocitada com predomínio de células mononucleadas. Nos animais sacrificados após 3 dias de tratamento notamos a presença de mioblastos, alguns miotubos e neovascularização. Quando analisamos os tecidos dos animais sacrificados após 7 dias de tratamento, observamos a presença de reorganização dos tecidos musculares. Nos animais sacrificados 14 dias após o tratamento, as fibras musculares mostram-se em avançado estado de regeneração. O aparecimento precoce de mioblastos e raras fibras necróticas, a partir do terceiro dia de aplicação, levam-nos a concluir que o fármaco tópico anti-inflamatório consegue atravessar a barreira de tecidos biológicos através da transmissão da energia ultra-sônica, e assim acelerar a reconstituição do tecido lesado. / Abstract: This work presents a series of referring results to the use of the transmission of topical pharmacs through ultrasonic waves (Phonophoresis) in a produced surgical injuries in previous in the tibialis anterior muscle of Wisttar rats. The used pharmac was hydrocortisone gel to 10%. We had been used, in these experiment 42 rats with 60 days years' old and 300,0 average weight of g ( 50,0 g). The animals had been submitted to the chirurgical injury in the right leg, in previous the tibiae muscle. After 24 hours the area of the injury was dealt with ultrasound with faceplate hydrocortisone gel to 10%. The used frequency was of 1,0 MHz and the intensity of 0,4 W/cm2, with a time of 1 minute of insomniac, during 14 days. After the therapeutically one applied the rats they had been sacrificed, the frost fixed and cut muscle in cryostat. The gotten blades had been stain by H/E, Gomori's Trichrome, Masson's Trichrome and Mallory's Trichrome to be photographed in Zeiss photomicroscope. The analyzed proceeding from the animals injured, treated with ultra-sound and hydrocortisone present: after 1 day of treatment, skeletal muscle staple fibers parted by the phagocyte incision already with predominance of mononuclear cells. After 3 days of treatment, in the sacrificed animals, it is noticed myoblasts, some multinucleated myofibers and new vessel. When one analyzes of the sacrificed animals after 7 days of treatment, observes it presence of reorganization of muscular. In the sacrificed animals 14 days after the treatment, visualizes muscular fibers in advanced state of regeneration. The precocious appearance of myoblasts and rare necrotic tissue as fibers to leaving of the third day of application of treatment lever to conclude that the topical pharmac obtained to cross the biological barrier through the transmission of the ultrasonic energy. Of this form the hydrocortisone is taken until the small farm of lesion. / Mestre

The overall objective of this thesis work was to develop new insights into the etiology of scleroderma, a human systemic autoimmune disease, by analyzing the autoantibodies to centrosome antigens that develop during the disease. Centrosomes are perinuclear organelles that form microtubule arrays, including mitotic spindles that ensure the faithful segregation of chromosomes during mitosis. These studies used a novel methodology to determine the prevalence of anti-centrosome autoantibodies in patients with scleroderma. Recombinant centrosome antigens were used to determine the antigenic specificity of anti-centrosome antibody subsets by immunoblotting. Centrosome marker antibodies were used in indirect immunofluorescence assays to distinguish centrosomes within the polymorphic staining pattern frequently given by scleroderma sera. We found that 43% of patients are autoreactive to centrosomes, a prevalence higher than has been reported for any other scleroderma autoantigen. Half of the centrosome-positive patients also had autoantibodies against other antigens used in scleroderma diagnosis. However, in the remaining half of these patients, anti-centrosome antibodies represented the sole class of autoantibodies that was detectable. Anti-centrosome antibodies were detected in only a small percentage of normal individuals and patients with other connective tissue diseases. These data suggest that anti-centrosome autoantibodies may represent a new diagnostic tool in scleroderma. Upon examination of anti-centrosome autoantibody development in an animal model, it appeared that this autoantibody specificity may develop in mice as a consequence of an infection. An infectious agent was isolated by plaque-formation from carrier mice. Further characterization of the infectious agent was undertaken to obtain information on its physical, morphological and cytopathological properties. The infectious agent was identified by sequence and unique antigenic properties to be homologous to the pig pathogen Mycoplasma hyorhinis. When reintroduced into naive mice, the murine mycoplasma triggered anti-centrosome autoantibody development. While anti-centrosome autoantibodies of IgM isotype are part of the repertoire of naive unimmunized mice, mycoplasma infection specifically triggered the development of anti-centrosome IgG. Moreover, centrosome autoreactivity was prevented by antibiotic treatment. The autoantibody response evolved to recruit additional specificities, having IgM isotypes, reactive to endoplasmic reticulum-associated autoantigens.

Made available in DSpace on 2014-06-11T19:31:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-27Bitstream added on 2014-06-13T19:01:54Z : No. of bitstreams: 1 araujo_gs_dr_arafo.pdf: 3177707 bytes, checksum: 59367ad75a2e6289695c38f3d0acbec0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo do presente estudo foi realizar uma avaliação histológica do efeito do laser de baixa intensidade (LBI) na resposta do tecido conjuntivo subcutâneo de camundongos ao implante dos tubos contendo cimento de óxido zinco e eugenol (OZE) Endofill, que foram irradiados imediatamente e 24 horas após o implante dos tubos. Foram utilizados sessenta camundongos (Mus muscullus albinus), distribuídos em 3 grupos (n=20): GI (controle), os animais receberam implante do tubo de polietileno com Endofill e não receberam a irradiação LBI; GII implante do tubo com Endofill e irradiação LBI vermelho (InGaAlP), λ685ηm, D=72J/Cm2, E=2J, T=58s, P=35mW; GIII implante do tubo com Endofill e irradiação LBI infravermelho (AsGaAl), λ830ηm, D=70J/Cm2, E=2J, T=40s, P=50mW. Os animais foram mortos nos períodos de 7 e 30 dias, os blocos de tecido foram seccionados com de 6μm de espessura e as lâminas foram coradas com: Hematoxilina e Eosina/Tricrômico de Masson, com o propósito de verificar as reações teciduais; Picrosírius para identificar o padrão de fibrose e Azul de Toluidina para quantificar os mastócitos. Os resultados foram analisados ao microscópio optico comum e de luz polarizada para a fibrose. A análise estatística realizada foi quali-quantitativa. A ação do LBI sobre o tecido conjuntivo diminuiu o efeito irritante oferecido pelo cimento Endofill, no período pós-operatório de 7 dias (P>0,05). Aos 30 dias ocorreu reparo tecidual, independente da irradiação do LBI. A irradiação LBI não ofereceu melhoria no padrão de fibrose, e proporcionou queda significativa de mastócitos independente do período estudado. / The aim of the present study was to perform a histological evaluation of the effect of the low level laser therapy (LLLT), in the response of the subcutaneous conjunctive tissue of mice to the tubes implant with to the zinc oxide and eugenol sealer (ZOE) Endofill, that were immediately irradiated and again 24h after the implant of the tubes. Sixty mice (Mus muscullus albinus) were used, distributed into 3 groups (n=20): GI (control), the animals received the polyethylene tube implant with the Endofill and no LLLT irradiation; GII, tube implant with the Endofill and red LLLT irradiation (InGaAIP), λ685ηm, D=72J/Cm2, E=2J, T=58s, P=35mW; GIII, tube implant with the Endofill and infrared LLLT irradiation (AsGaAl), λ830ηm, D=70J/Cm2, E=2J, T=40s, P=50mW. The animals were killed after 7 and 30 days; the blocks of tissue were cut into serial 6μm thick sections and glass slides were stained with: Hematoxylin and Eosin/with Masson Trichrome, in order to verify the tissue reactions; Picrosírius, to identify the fibrosis rate and Toluidine Blue, to quantify mast cells (MC). The results were analyzed through the normal use optical microscope and a polarized light one for fibrosis. The statistical analysis carried out was quali-quantitative. The action of the LLLT on the connective tissue reduced the irritating effect produced by the Endofill sealer, at the post-operative period of 7 days (P>0,05). In 30th days there was tissue repair independent of the irradiation of LLLT. The LLLT irradiation didn't offer an improvement of the fibrosis rate, and provided a significant fall in the concentration of MC independent of the studied period.

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-04-30Bitstream added on 2014-06-13T19:04:21Z : No. of bitstreams: 1 luize_ds_dr_araca.pdf: 3119615 bytes, checksum: 3282986a90405ad7117f1b9d2fd00c27 (MD5) / O objetivo do presente estudo foi avaliar, por meio de análise histológica e histométrica, o processo de reparo de defeitos de furca Classe II, em cães, criados cirurgicamente e tratados com enxerto de osso autógeno em neoformação (OAN) associado ou não a barreira de tecido conjuntivo (TC). Foram utilizados os 3os e 4os pré-molares mandibulares de 6 cães machos para a criação dos defeitos de furca. Inicialmente foram extraídos os 1os molares superiores, com o intuito de criar uma área de rebordo ósseo edêntulo. Após 28 dias, foram confeccionados alvéolos cirúrgicos nestas áreas, com finalidade de obter osso autógeno em neoformação. Decorridos 14 dias, os defeitos de furca classe II, com medidas de 5mm (altura) e 2mm (profundidade), foram criados cirurgicamente e tratados imediatamente. Os dentes foram distribuídos, por meio de randomização bloqueada, em 4 grupos experimentais (n=6): Grupo C (GC): defeito preenchido somente pelo coágulo sanguíneo; Grupo O (GO): preenchimento com OAN; Grupo B (GB): o defeito, preenchido pelo coágulo sanguíneo, foi recoberto por barreira de TC; e Grupo O/B (GO/B): preenchimento com OAN associado a barreira de TC. Os retalhos foram suturados de forma a cobrir totalmente os defeitos. A eutanásia dos animais foi realizada após 90 dias do tratamento dos defeitos de furca criados. Após remoção das peças e tratamento laboratorial de rotina, foram obtidos cortes histológicos seriados no sentido mésio-distal, corados com hematoxilina e eosina ou Tricrômico de Masson. Cinco cortes de cada dente foram selecionados, de forma a representar toda a extensão da furca, para as análises histológica e histométrica. Foram avaliadas medidas lineares e medidas de área da cicatrização periodontal. Os dados obtidos por meio... / The purpose of this study was to histologically and histometrically evaluate the healing of surgically created Class II furcation defects treated using an autogenous bone in neoformation (ABN) graft with or without a connective tissue graft (CT) barrier. The third and fourth mandibular premolars (P3 and P4) of six mongrel dogs were used in this study. Initially, the both first upper molars were extracted, aiming the establishment of an edentulous ridge. After 28 days, surgical alveolus was produced en these areas. After 14 days, Class II furcation defects (5 mm in height and 2 mm in depth) were surgically created and immediately treated. Teeth were randomly divided into four groups: Group C (GC), in which the defect was filled with blood clot only; Group AB (GAB), in which the defect was filled with ABN graft; Group CB (GCB), in which the defect, filled with blood clot, was covered by CT barrier; and Group AB/CB (GAB/CB), in which the defect was filled with ABN graft and covered by a CT barrier. Flaps were repositioned to cover all defects. The animals were euthanized 90 days post-surgery. Vestibule-lingual serial sections were obtained and stained with either hematoxylin and eosin or Masson’s trichrome. Histologic and histometric analyses, using a image-analysis software, were performed. Linear and area measurements of periodontal healing were evaluated and calculated as a percentage of the original defect for statistical analysis (analysis of variance; P <0.05). Histologically, the collagen fibers tending to a parallel direction, in groups treated with ABN graft. Although, in the GCB, the periodontal ligament seemed better organized. Anquilosis was observed in their groups that received ABN, whereas the epithelial migration was observed mainly in the specimens of the GC and GCB. The osseous bonefill of the furcation defect was... (Complete abstract click electronic access below)

Made available in DSpace on 2016-06-02T19:22:53Z (GMT). No. of bitstreams: 1 3146.pdf: 7150693 bytes, checksum: cd6c8d53b2bd8f45e723e67ca13309e2 (MD5) Previous issue date: 2010-03-12 / Financiadora de Estudos e Projetos / Tendons remodeling relies upon extracellular matrix restructuring by the matrix metalloproteinases (MMPs). The aim of this study was to investigate MMP-2 activity in different regions of the calcanear tendon after resistance training in ovariectomized rats. Wistar adult female rats were grouped into: sedentary (Sed-Intact); ovariectomized sedentary (Sed-Ovx); acute exercise (AcuteEx-Intact); ovariectomized acute exercise (AcuteEx-Ovx); resistance trained (ChronicEx-Intact) and ovariectomized resistance trained (ChronicEx-Ovx) (n= 10 each group). The resistance training protocol required the animals to climb a 1.1-m vertical ladder with weights attached to their tail was used. The sessions were performed once every 3 days with 4-9 climbs and 8-12 dynamic movements per scaling. The acute groups performed one session, and the chronic groups underwent a 12-week of resistance training. There was an increase in total MMP-2 activity in Sed- Ovx, AcuteEx-intact and ChronicExintact compared with Sed-Intact in the proximal region of calcanear tendon. AcuteEx-Ovx exhibited higher total MMP-2 than Sed-Ovx and AcuteEx-Intact in the distal region of calcanear tendon. Chronic-Ovx presented lower total MMP-2 activity than Sed-Ovx and Chronic-Intact in the distal region of tendon. The active MMP-2 was higher for the AcuteEx- Ovx than Sed-Ovx and AcuteEx-Intact in proximal region of tendon. There was higher active MMP-2 in the distal region of tendon in the Acute-Ovx than Sed-Ovx and AcuteEx-Intact. Ovariectomy and resistance exercise modulate MMP-2 activity according to specific tendon region, indicating a differentiated tissue remodeling. / O remodelamento dos tendões depende da re-estruturação da matriz extracelular realizada pelas metaloproteinases de matriz (MMPs). O objetivo deste estudo foi investigar a atividade da MMP-2 em diferentes regiões do tendão calcâneo de ratas após ovariectomia e treinamento resistido. Ratas adultas Wistar foram agrupadas em: sedentário (Sed-Intacto); sedentário ovariectomizado (Sed-Ovx); exercício agudo (AgudoEx-Intacto); exercício agudo e ovariectomizado (AgudoEx-Ovx); treinado resistido (CrônicoEx-Intacto) e ovariectomizado treinado resistido (CrônicoEx-Ovx) (n= 10 por grupo). O protocolo de treinamento resistido exigiu a escalada dos animais em uma escada vertical de 1.1 metros com pesos atados a suas caudas. A sessão foi realizada uma vez a cada três dias de 4 a 9 escaladas com 8 a 12 movimentos dinâmicos em cada escalada. Cada sessão de treinamento consistia de no mínimo quatro escalas, com 50%, 75%, 90% e 100% da capacidade máxima de carregamento do animal, determinada anteriormente. Durante as escaladas subseqüentes (máximo de cinco escaladas) eram adicionados 30g até que uma nova capacidade máxima de carregamento fosse atingida. Os grupos agudos realizaram apenas uma sessão e os animais dos grupos crônicos foram submetidos a 12 semanas de treinamento resistido. Foi observado na região proximal do tendão calcâneo aumento da atividade total da MMP-2 no Sed-Ovx, AgudoEx-Intacto, CrônicoEx-Intacto comparados com o Sed-Intacto (p&#8804;0,05). Na região distal do tendão calcâneo, o AgudoEx-Ovx exibiu maior atividade da MMP-2 total do que Sed-Ovx e AgudoEx-Intacto (p&#8804;0,05). O CrônicoEx-Ovx apresentou na região distal do tendão calcâneo menor atividade total da MMP-2 em relação ao Sed-Ovx e CrônicoEx-Intacto (p&#8804;0,05). O AgudoEx-Ovx apresentou na região proximal e distal do tendão calcâneo maiores valores na forma ativa da MMP-2 comparado ao Sed-Ovx e AgudoEx-Intacto (p&#8804;0,05). Ovariectomia e treinamento resistido modulam a atividade da MMP-2 de acordo com a região específica do tendão calcâneo.

Cancer cells are most clearly characterized by their abnormal and uncontrolled cell growth. One of the most notable theories that explains the vast proliferative capacity of tumorigenic cells is the Warburg effect, a significant shift in metabolism wherein cancer cells preferentially fuel cell division using aerobic glycolysis instead of aerobic respiration. This upregulation of glycolytic fermentation in aerobic environments is highly unusual - glycolysis is typically utilized in anaerobic conditions, but nonetheless dominates cancer metabolic activity in spite of the presence of oxygen. Since the discovery the Warburg effect in the 1920s, researchers have struggled to identify whether aerobic glycolysis is a cause or consequence of carcinogenesis. Interestingly, a new theory recently emerged that challenges this widely-accepted metabolic paradigm for cancer. Known as the reverse Warburg effect, this new mechanism shows that in carcinomas such as breast cancer, the Warburg effect occurs not in cancer cells, but rather in tumor-adjacent stromal fibroblasts. These cancer-associated fibroblasts (CAFs) in the greater tumor microenvironment produce lactate - a high-energy metabolite formed as a byproduct of aerobic glycolysis - to fuel aerobic respiration and rapid tumorigenesis in neighboring cancer cells. This emerging theory emphasizes the pivotal role of the tumor microenvironment in determining whether cancer cells undergo aerobic glycolysis or aerobic respiration. Central to this lactate-linked metabolic intersection are two critical enzymes that regulate a cell's metabolic commitment - lactate dehydrogenase (LDH) and pyruvate dehydrogenase complex (PDHc). In order to clarify the mechanisms through which CAFs induce tumorigenesis in breast cancer, we plan to carry out two specific aims: (1) evaluate the enzymatic activity of LDH and PDHc, and (2) compare LDH and PDHc enzyme content. Using co-culture techniques to study the breast cancer tumor microenvironment in vitro, we will compare the enzymatic activity and enzyme content of both MCF7 breast cancer cells and CAFs to identify whether the reverse Warburg effect occurs due to post-translational enzyme activation or increased enzyme synthesis.