Dissertations / Theses: 'Experimental tumor'

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Tore, Aas Alf. "Experimental brain tumor metabolism and therapy." Lund, Sweden : Dept. of Neurosurgey, University Hospital, 1994. http://books.google.com/books?id=4XlrAAAAMAAJ.

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Zarur, Jamil Martins. "Modelo experimental de quimioembolizaÃÃo hepÃtica." Universidade Federal do CearÃ, 2004. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=166.

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CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
OBJETIVO: Estabelecer um modelo de tumor no fÃgado de ratos para estudo do comportamento tumoral e avaliar o uso da quimiembolizaÃÃo transarterial. MÃTODOS: Utilizou-se oitenta e oito ratos Wistar, fÃmeas, adultos, pesando entre 175- 284 g . Realizado incisÃo abdominal de 3 cm e implantou-se o carcinossarcoma de Walker 256 no lÃbulo esquerdo do fÃgado. Dividiu-se em trÃs grupos que receberam respectivamente 100x 103 , 200x 103 e 300x 103 cÃlulas tumorais, avaliado a pega do tumor e a sobrevida. Em outro grupo de experimento com 39 animais inoculados com tumor de Walker foi avaliado a sobrevida dos animais apÃs infusÃo do 5-Flourouracil (5-FU) por via intra-peritoneal e intra-arterial. RESULTADOS: O implante do carcinossarcoma de Walker no fÃgado de ratos apresentou desenvolvimento de 100 %, teve um crescimento rÃpido e desenvolvimento de metÃstases tardiamente, levando os animais ao Ãbito entre o sÃtimo e dÃcimo quinto dia. A quimiembolizaÃÃo transarterial Ã possÃvel de ser realizada experimentalmente. O uso do 5-FU aumentou a sobrevida em comparaÃÃo ao grupo controle. CONCLUSÃO: O modelo de implante do tumor de Walker no fÃgado de ratos Ã eficiente, de fÃcil reprodutibilidade, e sobrevida mÃdia de 9,96Â0.3 dias. A quimioterapia transarterial hepÃtica pode ser realizada experimentalmente para avaliar diversas drogas.
PURPOSE: An animal model to study the behaviour of liver tumor in rat and its response after use of transarterial chemoembolization. METHODS: We use 88 Wistar rats, all of them were females, adult, weight 175-284 g. Abdominal incison of three cm and implanted the Walker carcinossarcoma 256 at left lobule of the liver. The animals were divided into three grups, that received 100x103 , 200x103, and 300x103 cells. Followed up the animas to avaliate life standing and tumoral development. In another experiment was used 39 animals which already had Walker 256 tumor and we study the survival of the animals after treatment with 5-FU IP or 5-FU IA. RESULTS: The orevall tumor development rate were 100%. Tumor growth was fast, and devolopment metastases on old fase. The animals dead between 7Â and 15Â day. Its possible to do chemoembolization experimentaly, after the use of 5-FU the rate survival increased. CONCLUSION: The model with Walker 256 tumor developed here is easy to repoduce, efficient, with high tumor development rate observed, the life standing is about 9,96 Â 0,3 days. The chemoembolization experiment allows to assess several drugs.

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Sheikholvaezin, Ali. "Recombinant antibodies and tumor targeting." Doctoral thesis, Umeå : Univ, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-875.

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Swarup, Arvind. "Experimental characterisation of the dielectric properties of tumor tissues." Thesis, University of Ottawa (Canada), 1987. http://hdl.handle.net/10393/5162.

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Morano, JosÃ AntÃnio Carlos Otaviano David. "AvaliaÃÃo dos efeitos da hipertermoterapia por ultrasom associada a agentes antiangiogÃnicos no tratamento do tumor experimental de walker." Universidade Federal do CearÃ, 2009. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4685.

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CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
Os mÃtodos tradicionais de tratamento do cÃncer, como a quimioterapia e a radioterapia, embora sejam eficazes em vÃrios tipos de tumores, encontram freqÃentemente populaÃÃes de cÃlulas neoplÃsicas resistentes, alÃm de apresentarem uma baixa margem de seguranÃa para os pacientes. A utilizaÃÃo da hipertermia associada Ã quimioterapia e/ou radioterapia jÃ se encontra fartamente relatada como vantajosa na literatura especializada, principalmente em pacientes portadores de cÃncer em estÃdio avanÃado, submetidos previamente aos mÃtodos clÃssicos de tratamento. A aplicaÃÃo de calor nos tecidos atravÃs de ultrassom contÃnuo torna mais Ãgil Ãste procedimento e com eficÃcia comprovada. O uso dos antiangiogÃnicos tambÃm vem sendo relatado como eficaz na literatura especializada e atualmente, a lista destas substÃncias vem aumentando consideravelmente. O estudo da aÃÃo da hipertermia associada a alguns agentes antiangiogÃnicos tem sido sugerida uma vez que os vasos tumorais ao encontrarem-se dilatados, nÃo promoverÃo a diminuiÃÃo da temperatura no tecido tumoral e, consequentemente, os efeitos desta associaÃÃo serÃo mais intensos do que no tecido normal devendo contribuir para a morte celular. Objetiva-se neste trabalho, avaliar o efeito antitumoral e antiangiogÃnico da hipertermia induzida por US isolada e combinada com etoricoxibe e pegaptanibe,no carcinossarcoma de Walker 256 implantado na tela subcutÃnea do dorso de ratos por meio de utilizaÃÃo do modelo experimental de hipertermoterapia por US assim como o estudo dos efeitos da hipertermia por US isolada e em combinaÃÃo com etoricoxibe e pegaptanibe,na angiogÃnese tumoral.O mÃtodo utilizado para o estudo teve inÃcio com o implante de cÃlulas de tumor de Walker 256 no dorso de ratos Wistar machos. Os animais foram tratados com hipertermia aplicada atravÃs de aparelho de ultrassom, mantida a nÃvel de 45o C durante cinco minutos no terceiro dia apÃs a inoculaÃÃo e tambÃm tratados com etoricoxibe e pegaptanibe por via oral e intraperitoneal respectivamente a partir do dia da inoculaÃÃo. Cada grupo de animais foi submetido a medidas do crescimento tumoral durante o perÃodo de 30 dias, assim como tambÃm Ã avaliaÃÃo da microdensidade vascular atravÃs de estudo mesoscÃpico fotogrÃfico, validado pelo estudo microscÃpico. A aplicaÃÃo do calor atravÃs de aparelho de ultrasom demonstrou eficiÃncia e agilidade A hipertermia, o etoricoxibe e o pegaptanibe, apresentaram capacidade antiangiogÃnica, expressada tanto pela curva de sobrevida, como pela avaliaÃÃo da microdensidade vascular. Particularmente, a hipertermia isoladamente apresentou um efeito antiangiogÃnico significativo tanto na curva de crescimento tumoral como na diminuiÃÃo da densidade microvascular. A associaÃÃo da hipertermia com o pegaptanibe, demonstrou uma eficiÃncia na diminuiÃÃo da densidade microvascular significativamente maior do que os demais grupos. O modelo de aplicaÃÃo de hipertermia gerada por um aparelho de ultrassom na modalidade contÃnua foi satisfatÃria, demonstrando ter sido efetiva tanto na diminuiÃÃo do crescimento tumoral, como na diminuiÃÃo da densidade microvascular.
The traditional methods of cancer treatment, like the chemotherapy and radiotherapy, even though they are effective in many types of tumours, they find frequently resistant neoplasic cellsâ population, beyond presenting a low security margin to the patients. The hyperthermia use associated to the chemotherapy and radiotherapy are plenty mentioned as profitable in the specialist literature, especially in patients with cancer in advanced stage, submitted previously to the classic methods of the treatment. The tissuesâ heat insertion through the continuous ultrasound becomes the procedure faster and with proved efficacy. The antiangiogenic use also is being related like effective in the specialist literature and, at this moment, the substancesâ list has grown vastly. The study of the hyperthermia action associated to antiangiogenic agents has been suggested, once the tumour vessels are dilated, would not promote the temperature reduction in the tumour vessels and, therefore, the effects of this association would be more intense than in the normal tissue, what might contribute to the death cell. The study objective is to evaluate the antitumor and antiangiogenic effect of the hyperthermia induced by isolated ultrasound and combined with etoricoxibe and pegaptanibe in the 256 Walker carcinossarcoma implanted in the subcutaneous back screen of mouse by using the hyperthermia experimental model by ultrasound, like the hyperthermia effects study by isolated ultrasound and linked with etoricoxibe and pegaptanibe, in the tumour angiogenesis. The method used describes the insertion of 256 Walker Tumour cells in the back of male Wistar mouse. The animals were treated with hyperthermia applied through the ultrasound equipment, kept to a 45Â C level during five minutes in the third day after the inoculation and also treated with etoricoxibe and pegaptanibe by oral and intraperitoneal respectively since the inoculation day. Each animal group was submitted to a tumour growth measurement during a period of 30 days, as well as also a vascular microdensity evaluation through a photographic mesoscopic study, validated by the microscopic study. The heat application through the ultrasound equipment demonstrated efficiency and agility. The hyperthermia, the etoricoxibe and the pegaptanibe showed antiangiogenic capacity, expressed by the over life curve, and also by the vascular microdensity evaluation. Particularly, the isolated hyperthermia showed a significative antiangiogenic effect in the tumour growth curve and also in the decreasing of the micro vascular density. The association between the hyperthermia and the pegaptanibe demonstrated a greater efficiency in the reducing of the micro vascular density than the other groups. The hyperthermia application model generated by the ultrasound equipment in the continuous modality was satisfactory, demonstrating by being effective as much in the reducing of the tumour growth as in the decreasing of the micro vascular density.

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Hogerlinden, Max van. "NF-kB in epidermal signal transduction and tumor development /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-383-x/.

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Andreatta-Van, Leyen Sheila. "Experimental approaches for enhancing wound healing and inhibiting tumor growth." Case Western Reserve University School of Graduate Studies / OhioLINK, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1061557930.

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Oliveira, Paulo Ferdinando de Melo. "AvaliaÃÃo da hipertermoterapia associada ao Paclitaxel, 5-Fluorouracil e 5-Fluorouracil mais Ãcido FolÃnico no Tumor de Walker 256 implantado em estÃmagos de rato." Universidade Federal do CearÃ, 2003. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=393.

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
IntroduÃÃo: As drogas quimioterÃpicas convencionais nÃo tÃm obtido sucesso no tratamento do cÃncer gÃstrico. O paclitaxel (TaxolÂ) mostrou ser efetivo no tratamento dos cÃnceres de ovÃrio, mama e pulmÃo. O 5-fluorouracil (5-FU) tem apresentado resultados promissores no tratamento do cÃncer de cÃlon. O Ãcido folÃnico (LeucovorinÂ) potencializa a citotoxicidade do 5-fluorouracil. Estudos desen-volvidos no JapÃo, Estados Unidos e Europa vÃm sugerindo o uso de quimioterapia associada Ã hiper-termia no controle da doenÃa localmente avanÃada. Objetivos: Avaliar a influÃncia do paclitaxel, 5-fluorouracil e 5-fluorouracil mais Ãcido folÃnico, isolados e associados Ã hipertermia, na sobrevida de ratos com tumor de Walker 256 implantados no estÃmago, e observar o comportamento do tumor de Walker 256 original implantado em estÃmagos de rato sem tratamento e submetidos aos tratamentos quimioterÃpicos propostos, associados Ã hipertermia. MÃtodos: Implantou-se o tumor de Walker 256 na mucosa gÃstrica de rato no 3o, 7o, e 10o dias de inoculaÃÃo do tumor. Os animais foram tratados com paclitaxel, 5-fluorouracil e 5-fluorouracil mais Ãcido folÃnico, isolados e associados Ã hipertermia. Foram administrados paclitaxel na dose de 25 mg/m2, 5-fluorouracil na dose de 130 mg/m2 e Ãcido folÃnico na dose de 7 mg/m2. A Hipertermia de Corpo Inteiro foi iniciada 2 horas apÃs a administraÃÃo dos quimioterÃpicos, tendo duraÃÃo de 1 hora. Resultados: Os animais inoculados com tumor apresentaram uma sobrevida de 13,25 Â 0,53. Os animais tratados com Paclitaxel isolado apresentaram sobrevida de 28,61 Â 0,82; 20,92 Â 1,77 e 20,07 Â 0,60 no 3o, 7o e 10o dias, respectivamente, e aqueles trata-dos com Paclitaxel + hipertermia apresentaram sobrevida de 19,17 Â 1,20; 22,54 Â 1,47 e 17,92 Â 1,06 nos mesmos perÃodos. Os animais tratados com 5-fluorouracil isolado apresentaram sobrevida de 16,16 Â 0,52; 15,57 Â 0,57 e 17,94 Â 0,46 no 3o, 7o e 10o dias, respectivamente, e aqueles tratados com 5-fluorouracil + hipertermia apresentaram sobrevida de 14,45 Â 0,36; 16,36 Â 0,81 e 18,37 Â 1,86 nos mesmos perÃodos. Os animais tratados com 5-fluorouracil + Ãcido folÃnico apresentaram sobrevida de 14,89 Â 0,71; 16,56 Â 0,91 e 16,11 Â 0,67 no 3o, 7o e 10o dias, respectivamente, e aqueles tratados com 5-fluorouracil + Ãcido folÃnico + hipertermia apresentaram sobrevida de 17,60 Â 1,22; Â15,42 Â 0,31 e 15,45 Â 0,39 nos mesmos perÃodos. ConclusÃes: O tumor experimental de Walker 256 Ã um tumor de pequenas cÃlulas. A hipertermia associada Ã quimioterapia, com paclitaxel, 5-fluorouracil, 5-fluorouracil mais Ãcido folÃnico como tratamento do tumor de Walker experimental implantado nos estÃmagos de rato Wistar, nÃo melhorou a sobrevida.
Introduction: The conventional chemotherapy drugs have not obtained success on the treatment of gastric cancer. The paclitaxel (TaxolÂ) showed to be effective on treating lung, breast and ovarian cancer. The 5-fluorouracil (5-FU) has shown promising results on the treatment of colon cancer. The folinic acid (LeucovorinÂ) reinforces the 5-FU cytotoxicity. Studies developed in Japan, United States and Europe suggest the use of chemotherapy associated with hyperthermia on the control of locally advanced disease. Objectives: Evaluate the influence of paclitaxel, 5-fluorouracil and 5-fluorouracil plus folinic acid, isolated and associated with hyperthermia, on the survival of rats with Walker 256 tumor implanted on their stomach, and observe the behavior of the original Walker 256 tumor implanted in the stomach of rats with no treatment and with the proposed chemotherapy treatments associated with hyperthermia. Methods: The Walker 256 tu-mor was implanted on the mucous layer of the rat stomach on the 3rd, 7th and 10th day after inoculation. The animals were treated with paclitaxel, 5-fluorouracil and 5-fluorourcil plus folinic acid isolated and associated with hyperthermia. Paclitaxel 25 mg/m2, 5-fluorouracil 130 mg/m2 and folinic acid 7 mg/m2 were used. The Whole-Body Hyperthermia was initiated 2 hours after the administration of the chemotherapic drugs, with 1 hour of duration. Results: The animals in-oculated with tumor showed a survival of 13.25 Â 0.53. The animals treated with Paclitaxel isolated showed a survival of 28.61 Â 0.82; 20.92 Â 1.77 and 20.07 Â 0.60 in the 3rd, 7th and 10th days, respectively, and those treated with Paclitaxel + hyperthermia showed a survival of 19.17 Â 1.20; 22.54 Â 1.47 and 17.92 Â 1.06 in the same periods. The animals treated with 5-fluorouracil isolated showed a survival of 16.16 Â 0.52; 15.57 Â 0.57 and 17.94 Â 0.46 in the 3rd, 7th and 10th days, respectively, and those treated with 5-fluorouracil + hyperthermia showed a survival of 14.45 Â 0.36; 16.36 Â 0.81 and 18.37 Â 1.86 in the same periods. The animals treated with 5-fluorouracil + folinic acid showed a survival of 14.89 Â 0.71; 16.56 Â 0.91 and 16.11 Â 0.67 in the 3rd, 7th and 10th days, respectively, and those treated with 5-fluorouracil + folinic acid + hyperthermia showed a survival of 17.60 Â 1.22; 15.42 Â 0.31 and 15.45 Â 0.39 in the same periods. Conclusions: The Walker 256 is a small cell tumor. The hyperthermia associated with chemotherapy using pacli-taxel, 5-fluorouracil and 5-fluorouracil plus folinic acid as treatment of Walker experimental tu-mor implanted in Wistar rat stomachs do not improved the survival.

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Erlandsson, Ann. "Interaction studies of idiotypic and antiidiotypic antibodies at experimental tumor targeting /." Umeå : Klinisk mikrobiologi, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-583.

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Pedro, Renato Nardi. "Uso da nanopartícula de ouro ligada a moléculas de fator alfa de necrose tumoral como adjuvante da termoablação por radiofrequência de tumores renais = modelo animal experimental." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310676.

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Orientadores: Marcelo Lopes de Lima, Nelson Rodrigues Netto Junior
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O tratamento definitivo das massas renais malignas é primordialmente cirúrgico, sendo a nefrectomia radical eleita por muitos anos a cirurgia padrão para o tratamento do câncer renal localizado. Entretanto, com o envelhecimento populacional, maiores são as preocupações em se manter a capacidade funcional dos órgãos e sistemas do corpo humano. Portanto, a necessidade de se preservar tecido renal sadio durante o tratamento do câncer renal localizado, com auxílio de cirurgias parciais poupadoras de néfrons, se tornou imperativa. O tratamento de lesões renais sólidas pequenas passou a ter diferentes formas de abordagem, que variam desde técnicas de termoablação percutânea ou laparoscópica, nefrectomia parcial laparoscópica e aberta à até tradicional nefrectomia radical aberta. O uso de modalidades de tratamento cirúrgico com mínimo grau de agressão passou a ganhar atenção, devido à rápida recuperação do paciente, ao menor risco de complicações cirúrgicas e aos bons resultados oncológicos. Ablação por radiofreqüência (ARF) tem se mostrado um meio eficiente no tratamento de tumores renais pequenos e exofiticos. Atualmente, sua indicação é restrita a lesões de até 4 cm. O presente estudo foi montado para avaliar o uso conjunto da nanopartícula de ouro e fator alfa de necrose tumoral (TNF alfa) à ARF no tratamento de um modelo experimental de tumor renal. Materiais e Métodos: Trinta e sete coelhos brancos da raça New Zealand tiveram implantados em seus rins, através de uma laparotomia, um fragmento de 1 mm3 de tumor VX-2. Após 14 dias do implante, quando seus rins haviam desenvolvido uma lesão tumoral sólida menor que 1 cm, os animais foram divididos em 3 grupos de 10 e 1 grupo de 7 integrantes (sham) de acordo com o tratamento selecionado para o tumor renal focal: 1) Nanopartícula com TNF alfa; 2) Ablação por radiofreqüência; 3) Nanopartícula com TNF alfa seguido de Ablação por radiofreqüência; 4) Grupo sham. Todos os animais foram submetidos a mesma cronologia de tratamento, composta por 2 laparotomias e eutanásia. Os grupos tratados com as nanopartículas de ouro com fator alfa de necrose tumoral isolada ou complementarmente, as receberam 4 horas antes do procedimento cirúrgico na dose de 200 µm/Kg. A análise de resultados foi realizada com medidas macroscópicas e microscópicas do volume da área de ablação ou tumoral, segundo a fórmula do volume de uma elipsóide. Avaliação estatística foi realizada com Teste T Student, sendo considerado significante p<0.05. Resultados: O grupo que recebeu a nanopartícula com fator alfa de necrose tumoral e depois foi submetido à ARF apresentou maior zona de morte celular completa quando comparado ao grupo tratado somente com ablação por radiofreqüência (0.30 ± 0.07 vs 0.23 ± 0.03 mL, P=.03). A zona de transição foi menor no grupo que recebeu a nanopartícula com fator alfa de necrose tumoral e ablação por radiofreqüência quando comparada ao grupo tratado somente com ablação por radiofreqüência (0.08 ± 0.02 vs 0.13 ± 0.05 mL, P =.01). Conclusão: O presente estudo demonstrou que o uso da nanopartícula de ouro com TNF alfa sensibiliza o insulto térmico sofrido por tumores sólidos decorrentes da ablação por radiofreqüência
Abstract: Radical nephrectomy has long been considered as gold standard treatment for localized renal tumors. However due to an increase in life expectation, organ sparing surgeries have emerged with the purpose of preserving as much healthy tissue as possible. Therefore, nephron sparing surgeries have become another valid option for localized renal tumors. There are different modalities of nephron sparing procedures, including open partial nephrectomy, laparoscopic nephrectomy and termoablative procedures. The later is associated with less morbidity and fast patient recovery. Radiofrequency ablation (RFA) is a well-known termoablative procedure and it has been most effective when the tumors are small, exophytic, and away from vital structures. The present study was designed to analyze the adjuvant use of gold nanoparticle with tumor necrosis factor alpha prior to radiofrequency ablation in a translational model of localized renal tumor. Material and Methods: A total of 37 New Zealand White rabbits had VX-2 tumors implanted into their kidneys; they were allowed to grow for 14 days, when a tumor mass of less than 1 cm could be detected. The animals were then split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits as follows: (1) Tumor necrosis factor alpha plus nanoparticle, (2) Radiofrequency ablation, (3) Tumor necrosis factor alpha nanoparticle (200 µm/Kg) followed 4 hours later by radiofrequency ablation. All groups were subjected to the same milestones of the experiment which was comprised of 2 laparotomies and sacrification. Gross and microscopic measurements of the ablation size as well as histological analysis using hematoxylin and eosin staining were performed to determine the effect of TNF alpha nanoparticle on the ablation. Statistical analysis was performed with Student's T test, considering p < 0.05 as significant. Results: The RFA plus TNF alpha nanoparticle group had a larger zone of complete cell death than the RFA-only group (0.30 ± 0.07 vs 0.23 ± 0.03 mL, P=.03). The zone of partially ablated tissue was smaller in the RFA plus TNF alpha nanoparticle group than in the RFA-only group (0.08 ± 0.02 vs 0.13 ± 0.05 mL, P =.01). Conclusions: We have demonstrated the efficacy of TNF alpha nanoparticle in enhancing RFA in a translational kidney tumor model. The potential usage of TNF alpha nanoparticle to improve RFA of renal cell carcinoma merits further study
Doutorado
Fisiopatologia Cirúrgica
Doutor em Ciências

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Nannmark, Ulf. "Tumour cell rheology experimental studies in vivo and in vitro on factors influencing tumor cell lodgement and survival in microvessels /." Göteborg : Dept. of Anatomy, University of Göteborg, 1992. http://books.google.com/books?id=9PhpAAAAMAAJ.

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Kiebish, Michael Andrew. "Mitochondrial lipidome and genome alterations in mouse brain and experimental brain tumors." Thesis, Boston College, 2008. http://hdl.handle.net/2345/27.

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Thesis advisor: Thomas N. Seyfried
Mitochondria are the key regulators of the bioenergetic state of the cell. Damage to mitochondrial protein, DNA, or membrane lipids can result as the cause or affect of disease pathology. Regardless, this damage can impair mitochondrial function resulting in a decreased ability to produce ATP to support cellular viability. This thesis research examined the mitochondrial lipidome by shotgun lipidomics in different populations of C57BL/6J (B6) brain mitochondria (non-synaptic and synaptic) and correlated lipid changes to differences in electron transport chain (ETC) activities. Furthermore, a comparison was made for non-synaptic mitochondria between the B6 and the VM mouse strain. The VM strain has a 1.5% incidence of spontaneous brain tumors, which is 210 fold greater than the B6 strain. I determined that differences in the brain mitochondrial lipidome existed in the VM strain compared to the B6 strain, likely corresponding to an increased rate of spontaneous brain tumor formation. Analysis of the mitochondrial genome in the CT-2A, EPEN, VM-NM1, and VM-M3 brain tumors compared to their syngeneic controls mouse strains, C57BL/6J (B6) and VM mice, was examined to determine if mutations existed in experimental brain cancer models. No pathogenic mtDNA mutations were discovered that would likely cause a decrease in the mitochondrial functionality. A novel hypothesis was devised to examine the tumor mitochondrial lipidome to determine if quantitative or molecular species differences existed that could potentially alter the functionality of the ETC. Brain tumor mitochondria were examined from tumors grown in vivo as well as in vitro. Numerous lipid differences were found in the mitochondria of brain tumors, of which the most interesting involved the unique molecular speciation of cardiolipin. ETC activities were significantly decreased in the primary ETC complexes which contribute protons to the gradient as well as the linked complexes of brain tumor mitochondria compared to controls. Taken together, it is likely that differences in the mitochondrial lipidome of brain tumors results in severe impairment of the mitochondria’s ability to produce ATP through the ETC. This research has provided a new understanding of the role of mitochondrial lipids in brain as well as brain cancer and offers an alternative explanation for metabolic dysfunction in cancer
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology

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Praxedes, Layanny Kelly Silveira. "Desenvolvimento de terapia alternativa usando adjuvantes nanoestruturados para o tratamento de tumor experimental." Universidade Federal de Goiás, 2016. http://repositorio.bc.ufg.br/tede/handle/tede/5990.

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Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
The capacity of the tumor has not present as immunogenic to the immune system is one of its escape mechanisms. The aim of this study was to evaluate the use of nanoparticles formed from poly Lactic-co-glycolic acid (PLGA) associated with aluminum hydroxide may potentiate the effect of these on the resolution of the tumor. Balb/c mice inoculated with Sarcoma 180 tumor cells were distributed into nine groups for the implementation of the various immunotherapeutic treatments involving the use of aluminum hydroxide, PLGA nanoparticles, and activated macrophages. The evaluation of the treatment was performed by analysis of the tumor, considering the weight reduction of the dissected tumor, morphological and histological analysis, and analysis of pro-inflammatory and immunosuppressive cytokines in the serum of mice. The group of mice treated with PLGA nanoparticle associated with aluminum hydroxide caused a significant regression of the tumor (p = 0.039) compared with untreated mice. The treatment involving macrophages and PLGA nanoparticles showed significant tumor regression compared to the group treated only with macrophages (p = 0.021). The groups that had significant tumor regression have high levels of IFN--4 and IL-10, differing from the profile found in the other groups. In the other treatments tested there was a reduction of the tumor mass, but without significant statistical results, and without changes in the levels of cytokines measured in the serum of animals. Therefore, it is believed that PLGA nanoparticle by their ability to release hydroxide in target cells controlled manner, can enhance the action of the adjuvant aluminum hydroxide. Further studies are needed to elucidate the mechanisms involved in this phenomenon, which support the other investigations
A capacidade do tumor de não se apresentar como imunogênico ao sistema imune constitui um dos seus mecanismos de escape. O objetivo do presente trabalho foi avaliar se o uso de nanopartículas formadas a partir de co-polímeros de ácido láctico-co-glicólico (PLGA), associada ao hidróxido de alumínio poderia potencializar o efeito destes na resolução do tumor. Camundongos Balb/c inoculados com células tumorais de Sarcoma 180 e distribuídos em nove grupos para a realização dos diferentes tratamentos imunoterápicos, envolvendo a utilização de hidróxido de alumínio, nanopartículas de PLGA e macrófagos ativados. A avaliação dos tratamentos foi realizada pela análise do tumor, considerando a redução do peso do tumor dissecado, análise morfológica e histopatológica e análise de citocinas pró-inflamatórias e imunossupressoras no soro dos camundongos. O grupo de camundongos tratados com nanopartículas de PLGA associadas ao hidróxido de alumínio promoveu uma regressão significativa do tamanho da massa tumoral (p = 0,039) comparado com camundongos não tratados. O tratamento envolvendo macrófagos e nanopartículas de PLGA apresentou uma regressão tumoral significativa comparada com o grupo tratado apenas com macrófagos (p = 0,021). Os grupos que tiveram regressão tumoral significativa apresentaram níveis elevados das citocinas IFN-, IL-4 e IL-10, diferenciando-se do perfil encontrado nos demais grupos. Nos outros tratamentos testados houve a redução da massa tumoral, porém sem resultados estatísticos significativos e sem grandes alterações nos níveis de citocinas dosados no soro dos animais. Logo, acredita-se que a nanopartícula de PLGA, por meio de sua capacidade de transporte e liberação do hidróxido nas células alvo de forma controlada, possa potencializar a ação do adjuvante hidróxido de alumínio. Outros estudos são necessários para a elucidação dos mecanismos envolvidos nesse fenômeno.

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Rodriguez, Alejandro. "Studies of Stroma Formation and Regulation in Human Pathological Conditions and in Experimental in vivo Models." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-120688.

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Fibrosis is a sequel of chronic inflammation and is defined as an excessive deposition of collagen that ultimately leads to organ dysfunction. To date there are no effective treatments for fibrosis. The main cell type involved in collagen deposition and organization is the myofibroblast. In the first study we examined how myofibroblasts differentiate in human fibrotic conditions and in experimental animal models. Human tissues were stained with antibodies that recognize integrin receptors and in addition we also stained for α-SMA, a myofibroblast marker. We found a co-localization between these two markers in stromal cells and hypothesized that integrin α1 is important for the acquisition of the myofibroblast phenotype. To tests this hypothesis we used knockout animals for this integrin subunit. These animals showed a reduction of α-SMA positive fibroblasts, indicating that the α1 integrin subunit is required for proper myofibroblast differentiation. In the second study we used a neuroblastoma tumor model to study tumour growth when a drug targeting the synthesis of cellular NAD was administered. In treated animals an expansion of the nonvascular stroma was observed compared to controls. Normalization of the vasculature was observed in treated tumors together with a decrease in hypoxia. Moreover, this was followed by a decrease in stromal PDGF-B and VEGF expression, suggesting a deactivation of the stroma. In the third study the effects of over-expression of the two pro-fibrotic growth factors TGF-β and PDGF-B in skin was evaluated. We observed that both growth factors induced fibrosis. Over time, a decrease in blood vessel density was observed in both treatment groups. Both factors also stimulated an expansion of the connective tissue cell population originating from the microvascular pericyte, but the phenotype of these cells differed in the different treatments with regards to expression of markers. Furthermore, in tissue over-expressing PDGF-B but not TGF-β, the fibrotic process was partially reversible.

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Guenther, Michael. "Cancer Therapy with Metronomically Scheduled Cyclophosphamide: Experimental Modalities within GDEPT and Tumor Escape Mechanisms." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-68423.

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Bohl, Kullberg Erika. "Tumor Cell Targeting of Stabilized Liposome Conjugates : Experimental studies using boronated DNA-binding agents." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3435.

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Jussila, Tommi. "Modelling cancer : recapitulation of tumor growth in experimental systems in vivo and in vitro /." Oulu : Oulun yliopisto, 2000. http://catalogue.bnf.fr/ark:/12148/cb40920259n.

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Buggey, Hannah. "Exploring the role of tumor necrosis factor-stimulated gene 6 in experimental ischaemic stroke." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/exploring-the-role-of-tumor-necrosis-factorstimulated-gene-6-in-experimental-ischaemic-stroke(383d1e5a-f0ee-49ef-8935-76d1ad83629e).html.

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Ischaemic stroke occurs as a result of a blockage in one of the brain’s arteries, leading to neuronal injury and death. Although stroke is a major cause of death and disability, there is no widely available treatment. Inflammation occurs in the brain and in the periphery following stroke, and both contribute to the ischaemic damage. Leukocytes such as neutrophils are key mediators of brain damage and inflammation, particularly in the presence of systemic inflammatory challenges such as interleukin-1 (IL-1). Tumor necrosis factor-stimulated gene 6 (TSG-6) is a potent inhibitor of neutrophil migration, and also modulates the immune response by dampening expression of cytokines and stabilising the extra-cellular matrix (ECM). Mesenchymal stem cells (MSCs) have shown immunomodulatory actions in many inflammatory conditions, and their benefit has often been attributed to the production of TSG-6. This work aimed to evaluate the potential of TSG-6 and TSG-6-expressing MSCs as therapies in cerebral ischaemia, and to investigate the expression profile of endogenous TSG-6 in response to stroke. Mice were subjected to middle cerebral artery occlusion (MCAo) followed by reperfusion. We investigated whether IL-1-induced acute brain injury after stroke is reversed by TSG-6, and long-term recovery was evaluated in mice treated with TSG-6 or MSCs. Functional outcomes were assessed, and brains were sectioned and stained for analysis of lesion volume, haemorrhagic transformation, blood-brain barrier (BBB) disruption and neutrophil infiltration. The expression profile of TSG-6 was evaluated in mice allowed to recover for 4h, 24h, 3, 5 or 7 days. TSG-6 expression was determined by quantitative PCR and immunohistochemistry. Treatment with TSG-6 reduced IL-1-induced neutrophil infiltration into the striatum, and led to decreased BBB disruption and haemorrhagic transformation at 24h. Treatment with TSG-6 in the absence of a systemic inflammatory challenge had no significant effect on lesion volume, BBB disruption or haemorrhagic transformation after 7 days reperfusion, however thalamic neutrophil infiltration was significantly reduced. Treatment with human MSCs had no significant effect on behavioural or histological outcomes, however a heightened inflammatory response in MSC-treated mice suggested rejection of the cells by the murine immune system. TSG-6 expression peaked in the ischaemic hemisphere at 5 days post-reperfusion, and was associated with astrocytes in the glial scar surrounding the infarcted tissue. TSG-6 might be a promising therapy for the treatment of stroke in the presence of systemic inflammation. TSG-6-expressing MSCs might provide a broader therapeutic potential, and further work should optimise experimental conditions to prevent rejection of the cells. Expression of TSG-6 within the glial scar suggests a potential role in repair and recovery following ischaemic stroke. Modulating the peripheral immune response remains an attractive and accessible therapeutic target for the treatment of cerebral ischaemia.

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Williams, K. J., M. R. Albertella, B. Fitzpatrick, Paul M. Loadman, Steven D. Shnyder, E. C. Chinje, B. A. Telfer, C. R. Dunk, P. A. Harris, and I. J. Stratford. "In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenograft." AACR Publications, 2009. http://hdl.handle.net/10454/4561.

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no
AQ4N (banoxantrone) is a prodrug that, under hypoxic conditions, is enzymatically converted to a cytotoxic DNA-binding agent, AQ4. Incorporation of AQ4N into conventional chemoradiation protocols therefore targets both oxygenated and hypoxic regions of tumors, and potentially will increase the effectiveness of therapy. This current pharmacodynamic and efficacy study was designed to quantify tumor exposure to AQ4 following treatment with AQ4N, and to relate exposure to outcome of treatment. A single dose of 60 mg/kg AQ4N enhanced the response of RT112 (bladder) and Calu-6 (lung) xenografts to treatment with cisplatin and radiation therapy. AQ4N was also given to separate cohorts of tumor-bearing mice 24 hours before tumor excision for subsequent analysis of metabolite levels. AQ4 was detected by high performance liquid chromatography/mass spectrometry in all treated samples of RT112 and Calu-6 tumors at mean concentrations of 0.23 and 1.07 microg/g, respectively. These concentrations are comparable with those shown to be cytotoxic in vitro. AQ4-related nuclear fluorescence was observed in all treated tumors by confocal microscopy, which correlated with the high performance liquid chromatography/mass spectrometry data. The presence of the hypoxic marker Glut-1 was shown by immunohistochemistry in both Calu-6 tumors and RT112 tumors, and colocalization of AQ4 fluorescence and Glut-1 staining strongly suggested that AQ4N was activated in these putatively hypoxic areas. This is the first demonstration that AQ4N will increase the efficacy of chemoradiotherapy in preclinical models; the intratumoral levels of AQ4 found in this study are comparable with tumor AQ4 levels found in a recent phase I clinical study, which suggests that these levels could be potentially therapeutic.

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Rocha, Michelle Corrêa da. "Investigação das propriedades citotóxicas e imunológicas de complexos de paládio(II) in vitro utilizando o modelo experimental de Ehrlich /." Araraquara : [s.n.], 2007. http://hdl.handle.net/11449/93597.

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Orientador: Iracilda Zeppone Carlos
Banca: Denise Fecchio
Banca: Ângela Maria Victoriano de Campos Soares
Resumo: O câncer destaca-se pela alta incidência e mortalidade. O tratamento do câncer compreende cada vez mais a quimioterapia combinada, ou seja, substâncias antitumorais agindo conjuntamente com as células do sistema imune, potencializando-as ou apenas mantendo-as viáveis para exercerem sua função. Dentre os tipos celulares que constituem o sistema imunológico, os macrófagos são apontados como os principais elementos do organismo de combate aos tumores. Os macrófagos ativados agem liberando produtos tais como radicais de oxigênio (H2O2) e nitrogênio (NO), interleucina-1ß (IL-1ß) e fator de necrose tumoral (TNF-a), que são prejudiciais às células tumorais dependendo da concentração, além de sua ação indireta através da secreção de interferon-gama (IFN-.). Complexos de paládio(II) são investigados há décadas, destacando-se por sua potencialidade como agente antitumoral. Neste trabalho avaliou-se a ação dos compostos [Pd(dmba)(X)(dppp)] (X= SCN, NCO, N3 ou Cl) sobre as células tumorais de Ehrlich e macrófagos in vitro, utilizando como padrão a cis-platina (cis-Pt). Para tanto, foram realizados ensaios para determinação do índice de citotoxicidade mediano, o IC50, para cada composto pelos períodos de 24 e 48h e com base em tais concentrações investigadas para os macrófagos verificou-se a produção e/ou inibição de NO e H2O2, além das citocinas TNF-a, IFN-. e IL-1 bem como a atividade citotóxica/citolítica. Os compostos demonstraram ser agentes promissores por seus efeitos sobre as células tumorais e imunes, muitas vezes de forma igual ou superior à cis-Pt, droga de uso corrente na quimioterapia do câncer.
Abstract: The cancer is a disease with high incidence and mortality. The cancer treatment involves the combinated chemotherapy wich one involves antitumour substances acting along with the immune cells, stimulating or only keeping them able to act in the immune response. Between the cell types that belong to the immunological system, the macrophages are considered the main elements of the body that can act against tumours. The activated macrophages act releasing substances like oxygen (H2O2) and nitrogen (NO) radicals, interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-á), wich are not beneficial to the tumour cells in some concentrations, besides its indirect action towards interferon-gama (IFN-ã) release. Palladium(II) complexes are employed in many studies to verify its antitumour properties. For example we can describe the four following compounds: [Pd(dmba)(X)(dppp)], X= SCN, NCO, N3 or Cl. This work had as goal the evaluation of the action of such compounds towards Ehrlich tumour cells, macrophages and lymphocytes in vitro, employing cis-platin (cis-Pt) as standard. The following parameters were evaluated: the cytotoxic index (IC50) of each compound after 24 and 48h incubation for Ehrlich tumour cells, macrophages and lymphocytes; the immunological behaviour of the compounds in the concentrations previously determined such as NO and H2O2 production or inhibition, besides the cytokines TNF-á, IFN-ã and IL-1 as well as the cytotoxic/cytolitic activity. The compounds presented a good behaviour, based on their efects towads tumour and immune cells, many times like or even better than cis-Pt, standard drug in cancer chemotherapy.
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21

Cabrera, Ortega Adriana Alicia [UNESP]. "Estudo da carcinogênese bucal experimental utilizando-se o óxido de nitroquinolina (4-NQO) em ratos." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/113930.

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O objetivo do presente trabalho foi validar as alterações teciduais e moleculares durante os estágios iniciais do processo de carcinogênese oral experimental em ratos, utilizando-se 4-NQO. Foram utilizados 20 ratos com aproximadamente 4 meses de idade, aleatoriamente separados em grupos controle (n=10) e tratados com solução de 50 ppm de 4-NQO dissolvido na água de beber (n=10). Os animais do grupo controle foram sacrificados no primeiro dia do experimento e os animais do grupo experimental foram sacrificados após 8 e 12 semanas de tratamento. Os cortes histológicos provenientes da língua foram corados por H&E ou submetidas à reação de imunohistoquímica para detecção de PCNA, Bcl-2, SOCS1 e -3 , e STAT3. Parte dos espécimes foi utilizada para a verificação da expressão de Vimentina, Cdh1, Cdh2 e TWIST1 por RT-qPCR. Os resultados demonstraram que o tratamento com 4-NQO após 8 semanas causou displasia epitelial severa e que houve exacerbação da atipia celular após 12 semanas de tratamento. A positividade dos anticorpos analisados, com exceção do STAT3, foi aumentada em ambos os períodos experimentais. Os resultados do presente estudo apontam que tratamento com 4-NQO por 8 ou 12 semanas viabiliza avaliar as displasias epiteliais experimentais tanto a nível morfológico quanto molecular.
The aim of this study was to validate the tissue and molecular changes during the early stages of experimental oral carcinogenesis in rats, using 4-NQO. Were used 20 rats with approximately 4 months of age, randomly divided into control group (n = 10) and treated with 50 ppm of 4- NQO solution dissolved in drinking water (n = 10). The control group animals were sacrificed on the first day of the experiment and the experimental rats were sacrificed after 8 and 12 weeks of treatment. Histological sections from the tongue were stained with H&E or subjected to immunohistochemistry analysis for detection of PCNA, Bcl – 2, SOCS1 and -3, and STAT3. Part of the specimens was used to verify the expression of vimentin, Cdh1, Cdh2 and TWIST1 by RT - qPCR. The results showed that treatment with 4-NQO after 8 weeks caused severe dysplasia and cellular atypia was exacerbation after 12 weeks of treatment. The positivity of antibodies analyzed, with the exception of STAT3 was increased in both experimental periods. The results of this study indicate that treatment with 4-NQO for 8 or 12 weeks enables evaluating experimental epithelial dysplasias both morphological as molecular level.

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22

Cabrera, Ortega Adriana Alicia. "Estudo da carcinogênese bucal experimental utilizando-se o óxido de nitroquinolina (4-NQO) em ratos /." Araraquara, 2014. http://hdl.handle.net/11449/113930.

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Orientador: Luiz Carlos Spolidorio
Banca: Helio Massaiochi Tanimoto
Banca: Silvana Regina Perez Orrico
Resumo: O objetivo do presente trabalho foi validar as alterações teciduais e moleculares durante os estágios iniciais do processo de carcinogênese oral experimental em ratos, utilizando-se 4-NQO. Foram utilizados 20 ratos com aproximadamente 4 meses de idade, aleatoriamente separados em grupos controle (n=10) e tratados com solução de 50 ppm de 4-NQO dissolvido na água de beber (n=10). Os animais do grupo controle foram sacrificados no primeiro dia do experimento e os animais do grupo experimental foram sacrificados após 8 e 12 semanas de tratamento. Os cortes histológicos provenientes da língua foram corados por H&E ou submetidas à reação de imunohistoquímica para detecção de PCNA, Bcl-2, SOCS1 e -3 , e STAT3. Parte dos espécimes foi utilizada para a verificação da expressão de Vimentina, Cdh1, Cdh2 e TWIST1 por RT-qPCR. Os resultados demonstraram que o tratamento com 4-NQO após 8 semanas causou displasia epitelial severa e que houve exacerbação da atipia celular após 12 semanas de tratamento. A positividade dos anticorpos analisados, com exceção do STAT3, foi aumentada em ambos os períodos experimentais. Os resultados do presente estudo apontam que tratamento com 4-NQO por 8 ou 12 semanas viabiliza avaliar as displasias epiteliais experimentais tanto a nível morfológico quanto molecular.
Abstract: The aim of this study was to validate the tissue and molecular changes during the early stages of experimental oral carcinogenesis in rats, using 4-NQO. Were used 20 rats with approximately 4 months of age, randomly divided into control group (n = 10) and treated with 50 ppm of 4- NQO solution dissolved in drinking water (n = 10). The control group animals were sacrificed on the first day of the experiment and the experimental rats were sacrificed after 8 and 12 weeks of treatment. Histological sections from the tongue were stained with H&E or subjected to immunohistochemistry analysis for detection of PCNA, Bcl - 2, SOCS1 and -3, and STAT3. Part of the specimens was used to verify the expression of vimentin, Cdh1, Cdh2 and TWIST1 by RT - qPCR. The results showed that treatment with 4-NQO after 8 weeks caused severe dysplasia and cellular atypia was exacerbation after 12 weeks of treatment. The positivity of antibodies analyzed, with the exception of STAT3 was increased in both experimental periods. The results of this study indicate that treatment with 4-NQO for 8 or 12 weeks enables evaluating experimental epithelial dysplasias both morphological as molecular level.
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23

Shah, Maulik Raj. "Tumor Immunity Following Adenovirus Mediated Herpes Simplex Thymidine Kinase Gene Transfer to Experimental Rat Gliomas." VCU Scholars Compass, 1997. https://scholarscompass.vcu.edu/etd/5302.

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Previous studies have determined adenovirus mediated herpes simplex thymidine kinase gene transfer (AV-TK) to be effective for the treatment of experimental gliomas. In this study we report three distinct phenomenon. First, animals with complete regression of subcutaneous tumors upon intratumoral injections of AV-TK with concomitant Ganciclovir® (GCV) administration developed tumor immunity. These animals had the ability to reject a subsequent inoculum of lethal doses of tumor cells. This tumor immunity was long standing and protective as far as 6 months from the time of initial tumor ablation. Of interest, adoptive transfer of splenocytes from AV-TK treated-tumor ablated animals to naive animals conferred resistance to tumor formation upon injection of lethal doses of tumor cells. This data strongly indicated the mechanism of tumor immunity was cell mediated. Further analysis of the anti-tumor immune response implicated CD8a83 cytotoxic T-lymphocytes as the effector cell. Animals with complete tumor regression survived over 300 days and showed no signs of tumor relapse. Therefore, treatment of solid unifocal tumors with AV-TK and GCV may be able to prevent tumor relapse through the generation of an anti-tumor immune response. Secondly, we determined that AV-TK and GCV treatment efficacy was dependent on tumor antigenicity. Two different subcutaneous tumor models were utilized; the weakly immunogenic 9L and the strongly immunogenic RT2. For the same dose of intratumorally injected AV-TK, a greater percentage of RT2 tumor were eliminated as compared to 9L. Final survival efficacy was dependant on the tumor type and the initial tumor size. In studying the importance of host immunity in tumor progression, we have determined that in vivo, the GCV mediated bystander effect was not sufficient to result in tumor eradication without involvement of a host immune response. In athymic rats, 9L tumors failed to regress upon AV-TK and GCV treatment. In contrast, tumors of similar size were ablated upon treatment in immunocompetent animals. Of related significance, adenovirus mediated gene transfer facilitated generation of tumor immunity. Animals with tumors ablated by AV-TK and GCV treatment developed an anti-tumor immune response which was protective against further tumor engraftment. In contrast, alternative treatments such as surgical excision of subcutaneous gliomas or tumor vaccination was not sufficient to protect against secondary tumor challenge. Injection of adenovirus altered the amount and phenotypes of tumor infiltrating lymphocytes from the NK phenotype towards tumor specific CD8+ CTL cells. This immunomodulatory property was potentially responsible for generation of the immune response. Therefore, AV-TK was effective through two mechanisms. Transfer of the HSVTK gene conferred GCV sensitivity resulting in substantial tumor regression and the adenovirus backbone served as an immune adjuvant to augment generation of host tumor immunity. This immunomodulatory property of adenovirus vectors is an added advantage to their use for cancer gene therapy.

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Petrellis, Maria Carla. "Avaliação dos efeitos do azul de metileno fotoativado no modelo experimental do Tumor de Walker 256." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-12122014-102820/.

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A TFD é considerada uma nova terapia minimamente invasiva destinada ao tratamento e destruição seletiva de diversos tipos de cânceres. Objetivo foi avaliar se os efeitos do azul de metileno fotoativado podem desencadear processos inflamatórios interferindo no desenvolvimento e na progressão tumoral. Os resultados demonstraram que o grupo tratado com 0.1% de azul de metileno+1J provocou um aumento estatísticamente significativo quando comparado em relação aos diferentes grupos tratados nos níveis e na expressão gênica dos diferentes marcadores inflamatórios, na geração EROS e MPO. Análise histológica complementou com os resultados anteriores, indicando que neste grupo há alterações morfológicas representadas por áreas de necrose na massa tumoral sólida com presença neutrofílica. Concluímos que há indícios que o tratamento 0.1% azul de metileno+ 1J foi capaz de gerar efeitos citotóxicos que por consequência aumentou a expressão dos mediadores inflamatórios promovendo inflamação e finalmente induzindo morte celular.
PDT is considered a new minimally invasive therapy for the treatment and selective destruction of various types of cancers. The objective was to evaluate the effects of methylene blue light activated may trigger inflammatory processes interfering with the development and tumor progression. The results showed that the group treated with 0.1 % methylene blue +1 J caused a statistically significant increase levels and gene expression of different inflammatory markers in ROS generation and MPO when compared at the different treat groups. Histological analysis complemented with previous results, indicating that there are morphological changes represented by areas of necrosis in the solid tumor mass with neutrophil presence in this group. We conclude that there is evidence that treatment 0.1 % methylene blue + 1J was able to generate cytotoxic effects therefore increased expression of inflammatory mediators, promoting inflammation and finally inducing cell death.

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Quilles, Marcela Bassi [UNESP]. "Atividade anti-tumoral e imunomodulatória de complexos de paládio (II) utilizando modelo experimental de Ehrlich." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/93609.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O câncer, manifestação originada pelo crescimento descontrolado de células, afeta milhões de indivíduos. Os macrófagos são as primeiras células a serem ativadas para participar de uma resposta imunológica propriamente dita, são células capazes de secretar mais de cem produtos biologicamente ativos, entre esses, espécies reativas de nitrogênio e citocinas que atuam no contexto da resposta imunológica e/ou inflamatória. Sabendo que compostos de paládio (II) podem apresentar potenciais atividades anti - tumorais, neste trabalho foram testado os compostos de fórmula geral [Pd(dmba)(Cl)tu] e [Pd(dmba)(N3)tu], nos quais dmba = N,N-dimetilbenzilamina e tu = tiouréia quanto a atividade antiinflamatória, antitumoral e mutagênica dos mesmos.Como droga padrão das reações realizadas foi utilizada a cis-platina. Foi determinada a ação destes compostos frente ao sistema imunológico através, de ensaios de determinação de citotoxicidade mediano (IC50) pela técnica de MTT, óxido nítrico (NO), peróxido de hidrogênio (H2O2), determinação das citocinas IL-1, IL-6, IL-12, TNF-α e IL-10. Além disso, foi determinado a atividade antitumoral dos compostos frente à célula tumoral de Ehrlich, assim como a atividade mutagênica pelo teste de Ames e Ensaio com plasmídio pUC 9.1. Os resultados mostraram produção de NO e das citocinas IL-1, IL-6, IL-12 e TNF-α; moderada produção de H2O2 pelos macrófagos peritoneais de animais normais e animais portadores do tumor de Ehrlich na sua forma sólida, estimulados com os compostos e seus ligantes, assim como a cis-platina. Por outro lado, de maneira contrária às outras citocinas testadas, não houve a produção de IL-10. No que se refere à atividade antitumoral dos compostos testados, estes mostraram efeito citotóxico sobre a linhagen tumoral testada. Com relação à atividade mutagênica, os compostos...
The cancer, manifestation originated by the growth not controlled of cells, affects million of individuals. Macrophages are the first cells to be activated to participate in an immune response itself, are cells to able to secreting more than one hundred biologically active products, among these, reactive nitrogen species and cytokines that act in the context of the immune response and / or inflammatory. Knowing that compounds of palladium (II) can be potential activities anti - tumor in this study was tested compounds of general formula [Pd (Pd) (Cl) tu] and [Pd (Pd) (N3) tu], where Pd = N, N-dimetilbenzilamina and tu = thiourea as the anti-inflammatory, antitumor and mutagenic of the same. As standard was used the cis-platinum. We determining the action of these compounds against the immune system, for tests to determine the median cytotoxicity (IC50) by the MTT technique, nitric oxide (NO), hydrogen peroxide (H2O2), determination of IL-1, IL-6 , IL-12, TNF-α and IL-10. Moreover, it was determined the antitumor activity of compounds against the Ehrlich tumor cell, as well as mutagenic by the Ames test and test with plasmid pUC 9.1. The results showed NO production and the IL-1, IL-6, IL-12 and TNF-α, by peritoneal macrophages from normal animals and animals with Ehrlich tumor in solid form was stimulated by the compounds and their ligands as well as cis-platinum. Moreover, in contrary manner to other cytokines tested, there wasn’t production of IL-10, and H2O2. With regard to the antitumor activity of the compounds tested, these showed cytotoxic effect on tumor lineage tested. With respect to mutagenic activity, compounds and ligands weren’t mutagenic in vitro, unlike cis-platinum was shown to be mutagenic, causing mutations in the DNA of Salmonella typhimurium by the Ames test. The compounds and ligants were not also to induce DNA breaks in the plasmid... (Complete abstract click electronic access below)

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26

Baba, Kiichiro. "Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect." Kyoto University, 2020. http://hdl.handle.net/2433/259722.

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27

Grenbäck, Eva. "Galanin in the pituitary and in human circulation : clinical and experimental studies /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-980-7/.

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Hultman, Bo. "Clinical and Experimental Studies in Peritoneal Metastases from Gastric Cancer." Doctoral thesis, Uppsala universitet, Kolorektalkirurgi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197776.

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Gastric cancer (GC) is one of leading causes of death in the world, and peritoneal metastases (PM) are a major site of recurrence. PM from GC implies a poor prognosis, with median overall survival (mOS) approximately 3 months and no survival at five years. The aims of this thesis were to explore the incidence and evaluate prognostic factors for mOS of PM from GC in a defined population; to investigate the outcome of a new multimodal treatment; to analyse the treatment costs, and to investigate differences in drug sensitivity between individual patient samples and between various tumours. The incidence of loco-regional advanced GC was 3.8 per 100,000 person-years. Synchronous loco-regional GC in combination with synchronous distant metastasis was a negative prognostic factor while chemotherapy and good performance status, and radiotherapy plus chemotherapy were positive prognostic factors . There were no significant differences in mOS for the group of patients included during the period 2000-2004 versus 2005-2009, and this lack of improvement in mOS during the past decade justifies new treatment approaches. In a Phase II study of patients treated with neoadjuvant systemic chemotherapy followed by cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, mOS was 14.3 months and for patients with macroscopically radical surgery mOS was 19.1 months. The mean overall cost of the loco-regional treatment was $145,700 compared to $59,300 with systemic chemotherapy treatment. In an ex vivo chemo-sensitivity test, it was determined that GC samples were equivalent to colorectal cancer in chemo-sensitivity to standard drugs and targeted drugs, whereas ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the drugs, arguing for individualized drug selection. The incidence of loco-regional advanced GC was more common than previously reported and there were no improvements in mOS over the past decade. The mOS for patients with neoadjuvant systemic chemotherapy followed by macroscopically radical cytoreductive surgery + hyperthermic intraperitoneal chemotherapy was better than in recent reports on treatment with systemic chemotherapy. Treatment of advanced GC patients is costly irrespective of treatment modality. The GC samples varied considerably between individuals in terms of sensitivity to increasing concentrations of the drugs and were comparable to colorectal cancer in chemo-sensitivity.

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Shiikh, Dahir Mahamed. "Effects of treatments with angiogenesis inhibitors on tumor stroma in animal experimental models of child cancer Neuroblastoma." Thesis, Uppsala universitet, Avdelningen för toxikologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-218148.

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Neuroblastoma, a neuroendocrine tumor, is the most common cancer in infancy. 75 % of those affected are under the age of 5. The disease is heterogeneous and survival rate is low. Current treatment of neuroblastoma consists of surgery, radiation and chemotherapy, where the targets for the treatment are the malign cells. Due to the cancer cells instable genome there is a risk for resistance development. This negatively impacts the treatments goal of hindering tumor growth and spread. Tumor growth is not only determined by malign cells but also the interactions of those tumor cells with tumor vessels and different types of cells in the tumor stroma. The aim of this paper is to develop a relevant histological method to study the properties of tumor stroma in tumor sections retrieved from human NB tumor xenografts in mice treated with angiogenesis inhibitors SU11657 and Zoledronic acid. The study is a continuation of previous studies with the inhibitors which have shown good effect on tumor growth and angiogenesis on neuroblastoma. In the short term treatment with SU11657 and Zoledron acid showed that tumor growth declined. In the longer treatment with SU11657 the growth didn’t decline with the same rate compared to the short term treatment. Angiogenesis on the other hand decreased in all the treatments independent of treatment duration. The histological staining with Sirius red revealed that treated tumors had an increased amount of stroma compared to the untreated tumors. In conclusion the relative increase of tumor volume, decreased number of vessels and expansion of tumor stroma in the longer treatment with SU11657 indicated that tumors might survive the angiogenesis inhibitor treatment through expansion/activation of its stroma. The histological staining with Sirius red in saturated picric acid marked the collagen, i.e. stroma, well and enabled quantification of the stroma.

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Chuang, Cynthia Fu-Yu. "Experimental evaluation and mathematical modeling of the pharmacokinetics of boronophenylalanine-fructose (BPA-f) in murine tumor models." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85315.

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Marshall, Aiden Christopher James 1976. "The role of Fas and TNFα in experimental autoimmune gastritis." Monash University, Dept. of Pathology and Immunology, 2003. http://arrow.monash.edu.au/hdl/1959.1/9413.

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Kholodnyuk, Irina. "A microcell hybrid based elimination test to identify human chromosome 3 regions that antagonize tumor growth /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-581-6/.

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Possebon, Ricardo Billig. "Investigação experimental da relação entre temperatura e impedância elétrica de biomaterial - fígado bovino e modelagem de ablação por radiofrequência para tratar tumor hepático." Universidade Federal do Pampa, 2016. http://dspace.unipampa.edu.br:8080/xmlui/handle/riu/786.

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O câncer é uma das principais causas de morte no mundo, matando mais de 8 milhões de pessoas por ano, isto faz com que essa doença se torne uma das piores de nossa geração e afetando milhares de famílias mundo afora. Nos países em desenvolvimento esses números se agravam, devido à detecção tardia da doença e a utilização de tratamentos convencionais, que muitas vezes são ineficazes e causam diversos efeitos colaterais. A ablação por radiofrequência (RFA) é um tratamento de combate ao câncer que utiliza energia térmica, gerada pela passagem de uma corrente elétrica a partir de um eletrodo inserido sobre o tumor, para matar as células cancerígenas. Este processo é minimamente invasivo e não apresenta efeitos colaterais significativos, fazendo com que o paciente possa ir para casa um dia após o procedimento. Visando ampliar e facilitar a utilização do RFA foi desenvolvido um software de modelagem matemática que utiliza elementos finitos para simular os resultados da ablação tumoral (RAFEM). Com o auxílio deste software os médicos serão capazes de otimizar os parâmetros do processo, tais como: voltagem, potência e o tempo de aplicação. Experimentos de RFA foram realizados para descobrir parâmetros que influenciam o processo, como a máxima temperatura atingida pelo eletrodo durante o processo. Descobriu-se que a temperatura na ponta do eletrodo ultrapassa os 100°C, causando a necrose do tecido nesta região. A relação entre a temperatura da superfície do eletrodo e tempo de aplicação obtido foi posteriormente utilizado como parâmetro de entrada no software para realizar as simulações. Os resultados obtidos foram validados através da comparação com os dados experimentais obtidos por Mulier et al. (2012). O software RAFEM mostrou-se eficaz na simulação dos efeitos causados pelo processo de RFA, tornando-se uma potencial ferramenta para auxiliar médicos e pacientes no tratamento de combate ao câncer.
Cancer is a leading cause of death worldwide, killing more than 8 million of people a year, making the cancer one of the worst of our generation and affecting thousands of families around the world. In developing countries these numbers become worse, since disease detection is later and only conventional treatments are used, which are often ineffective and cause many collateral effects. Radiofrequency ablation (RFA) is a treatment against cancer that applies thermal energy generated by passing electric current from an electrode inserted in the tumor to kill cancer cells. This procedure is minimally invasive and not presents significant collateral effects, so that the patient can go home one day after the treatment. Aiming to expand and facilitate the use of RFA, mathematical modeling software (RAFEM) that uses finite element method to simulate tumor ablation was developed. With the aid of this software doctors will be able to optimize the process parameters, such as voltage, power and application time. RFA experiments were performed to find out which parameters influence the process, such as the maximum temperature reached by the electrode during the process. It was found that the temperature at the electrode tip exceeds 100°C, causing tissue necrosis in the tip region. The relationship of the electrode surface temperature vs time was used as an input parameter of the software to perform the simulations. The results were validated by comparison with experimental data obtained by Mulier et al. (2015). The RAFEM software was proved to be effective in the simulation of the effects caused by the RFA process. This makes it to be a potential tool to assist doctors and patients in the treatment against cancer.

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Rocha, Michelle Corrêa da [UNESP]. "Investigação das propriedades citotóxicas e imunológicas de complexos de paládio(II) in vitro utilizando o modelo experimental de Ehrlich." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/93597.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Universidade Estadual Paulista (UNESP)
O câncer destaca-se pela alta incidência e mortalidade. O tratamento do câncer compreende cada vez mais a quimioterapia combinada, ou seja, substâncias antitumorais agindo conjuntamente com as células do sistema imune, potencializando-as ou apenas mantendo-as viáveis para exercerem sua função. Dentre os tipos celulares que constituem o sistema imunológico, os macrófagos são apontados como os principais elementos do organismo de combate aos tumores. Os macrófagos ativados agem liberando produtos tais como radicais de oxigênio (H2O2) e nitrogênio (NO), interleucina-1ß (IL-1ß) e fator de necrose tumoral (TNF-a), que são prejudiciais às células tumorais dependendo da concentração, além de sua ação indireta através da secreção de interferon-gama (IFN-.). Complexos de paládio(II) são investigados há décadas, destacando-se por sua potencialidade como agente antitumoral. Neste trabalho avaliou-se a ação dos compostos [Pd(dmba)(X)(dppp)] (X= SCN, NCO, N3 ou Cl) sobre as células tumorais de Ehrlich e macrófagos in vitro, utilizando como padrão a cis-platina (cis-Pt). Para tanto, foram realizados ensaios para determinação do índice de citotoxicidade mediano, o IC50, para cada composto pelos períodos de 24 e 48h e com base em tais concentrações investigadas para os macrófagos verificou-se a produção e/ou inibição de NO e H2O2, além das citocinas TNF-a, IFN-. e IL-1 bem como a atividade citotóxica/citolítica. Os compostos demonstraram ser agentes promissores por seus efeitos sobre as células tumorais e imunes, muitas vezes de forma igual ou superior à cis-Pt, droga de uso corrente na quimioterapia do câncer.
The cancer is a disease with high incidence and mortality. The cancer treatment involves the combinated chemotherapy wich one involves antitumour substances acting along with the immune cells, stimulating or only keeping them able to act in the immune response. Between the cell types that belong to the immunological system, the macrophages are considered the main elements of the body that can act against tumours. The activated macrophages act releasing substances like oxygen (H2O2) and nitrogen (NO) radicals, interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-á), wich are not beneficial to the tumour cells in some concentrations, besides its indirect action towards interferon-gama (IFN-ã) release. Palladium(II) complexes are employed in many studies to verify its antitumour properties. For example we can describe the four following compounds: [Pd(dmba)(X)(dppp)], X= SCN, NCO, N3 or Cl. This work had as goal the evaluation of the action of such compounds towards Ehrlich tumour cells, macrophages and lymphocytes in vitro, employing cis-platin (cis-Pt) as standard. The following parameters were evaluated: the cytotoxic index (IC50) of each compound after 24 and 48h incubation for Ehrlich tumour cells, macrophages and lymphocytes; the immunological behaviour of the compounds in the concentrations previously determined such as NO and H2O2 production or inhibition, besides the cytokines TNF-á, IFN-ã and IL-1 as well as the cytotoxic/cytolitic activity. The compounds presented a good behaviour, based on their efects towads tumour and immune cells, many times like or even better than cis-Pt, standard drug in cancer chemotherapy.

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Morano, José Antônio Carlos Otaviano David. "Avaliação dos efeitos da hipertermoterapia por ultrasom associada a agentes antiangiogênicos no tratamento do tumor experimental de Walker." reponame:Repositório Institucional da UFC, 2009. http://www.repositorio.ufc.br/handle/riufc/7711.

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MORANO, José Antônio Carlos Otaviano David. Avaliação dos efeitos da hipertermoterapia por ultrasom associada a agentes antiangiogênicos no tratamento do tumor experimental de Walker. 2009. 134 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2009.
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The traditional methods of cancer treatment, like the chemotherapy and radiotherapy, even though they are effective in many types of tumours, they find frequently resistant neoplasic cells’ population, beyond presenting a low security margin to the patients. The hyperthermia use associated to the chemotherapy and radiotherapy are plenty mentioned as profitable in the specialist literature, especially in patients with cancer in advanced stage, submitted previously to the classic methods of the treatment. The tissues’ heat insertion through the continuous ultrasound becomes the procedure faster and with proved efficacy. The antiangiogenic use also is being related like effective in the specialist literature and, at this moment, the substances’ list has grown vastly. The study of the hyperthermia action associated to antiangiogenic agents has been suggested, once the tumour vessels are dilated, would not promote the temperature reduction in the tumour vessels and, therefore, the effects of this association would be more intense than in the normal tissue, what might contribute to the death cell. The study objective is to evaluate the antitumor and antiangiogenic effect of the hyperthermia induced by isolated ultrasound and combined with etoricoxibe and pegaptanibe in the 256 Walker carcinossarcoma implanted in the subcutaneous back screen of mouse by using the hyperthermia experimental model by ultrasound, like the hyperthermia effects study by isolated ultrasound and linked with etoricoxibe and pegaptanibe, in the tumour angiogenesis. The method used describes the insertion of 256 Walker Tumour cells in the back of male Wistar mouse. The animals were treated with hyperthermia applied through the ultrasound equipment, kept to a 45º C level during five minutes in the third day after the inoculation and also treated with etoricoxibe and pegaptanibe by oral and intraperitoneal respectively since the inoculation day. Each animal group was submitted to a tumour growth measurement during a period of 30 days, as well as also a vascular microdensity evaluation through a photographic mesoscopic study, validated by the microscopic study. The heat application through the ultrasound equipment demonstrated efficiency and agility. The hyperthermia, the etoricoxibe and the pegaptanibe showed antiangiogenic capacity, expressed by the over life curve, and also by the vascular microdensity evaluation. Particularly, the isolated hyperthermia showed a significative antiangiogenic effect in the tumour growth curve and also in the decreasing of the micro vascular density. The association between the hyperthermia and the pegaptanibe demonstrated a greater efficiency in the reducing of the micro vascular density than the other groups. The hyperthermia application model generated by the ultrasound equipment in the continuous modality was satisfactory, demonstrating by being effective as much in the reducing of the tumour growth as in the decreasing of the micro vascular density.
Os métodos tradicionais de tratamento do câncer, como a quimioterapia e a radioterapia, embora sejam eficazes em vários tipos de tumores, encontram freqüentemente populações de células neoplásicas resistentes, além de apresentarem uma baixa margem de segurança para os pacientes. A utilização da hipertermia associada á quimioterapia e/ou radioterapia já se encontra fartamente relatada como vantajosa na literatura especializada, principalmente em pacientes portadores de câncer em estádio avançado, submetidos previamente aos métodos clássicos de tratamento. A aplicação de calor nos tecidos através de ultrassom contínuo torna mais ágil êste procedimento e com eficácia comprovada. O uso dos antiangiogênicos também vem sendo relatado como eficaz na literatura especializada e atualmente, a lista destas substâncias vem aumentando consideravelmente. O estudo da ação da hipertermia associada a alguns agentes antiangiogênicos tem sido sugerida uma vez que os vasos tumorais ao encontrarem-se dilatados, não promoverão a diminuição da temperatura no tecido tumoral e, consequentemente, os efeitos desta associaçào serão mais intensos do que no tecido normal devendo contribuir para a morte celular. Objetiva-se neste trabalho, avaliar o efeito antitumoral e antiangiogênico da hipertermia induzida por US isolada e combinada com etoricoxibe e pegaptanibe,no carcinossarcoma de Walker 256 implantado na tela subcutânea do dorso de ratos por meio de utilização do modelo experimental de hipertermoterapia por US assim como o estudo dos efeitos da hipertermia por US isolada e em combinação com etoricoxibe e pegaptanibe,na angiogênese tumoral.O método utilizado para o estudo teve início com o implante de células de tumor de Walker 256 no dorso de ratos Wistar machos. Os animais foram tratados com hipertermia aplicada através de aparelho de ultrassom, mantida a nível de 45o C durante cinco minutos no terceiro dia após a inoculação e também tratados com etoricoxibe e pegaptanibe por via oral e intraperitoneal respectivamente a partir do dia da inoculação. Cada grupo de animais foi submetido a medidas do crescimento tumoral durante o período de 30 dias, assim como também á avaliação da microdensidade vascular através de estudo mesoscópico fotográfico, validado pelo estudo microscópico. A aplicação do calor através de aparelho de ultrasom demonstrou eficiência e agilidade A hipertermia, o etoricoxibe e o pegaptanibe, apresentaram capacidade antiangiogênica, expressada tanto pela curva de sobrevida, como pela avaliação da microdensidade vascular. Particularmente, a hipertermia isoladamente apresentou um efeito antiangiogênico significativo tanto na curva de crescimento tumoral como na diminuição da densidade microvascular. A associação da hipertermia com o pegaptanibe, demonstrou uma eficiência na diminuição da densidade microvascular significativamente maior do que os demais grupos. O modelo de aplicação de hipertermia gerada por um aparelho de ultrassom na modalidade contínua foi satisfatória, demonstrando ter sido efetiva tanto na diminuição do crescimento tumoral, como na diminuição da densidade microvascular.

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36

Jussila, T. (Tommi). "Modelling cancer: recapitulation of tumor growth in experimental systems in vivo and in vitro." Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514256433.

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Abstract The purpose of the study was to evaluate model systems of cancer development and compare some of their critical features with cancer development in vivo. Ovarian and endometrial cancers in man were used as correlates. Tumor development in experimental animals, exposed to carcinogens and UV irradiation, showed the entire spectrum of tumor development as compared to spontaneous carcinomas: hyperplasia, dysplasia, benign papillomas and malignant squamous cell carcinomas. For short-term analysis of differentiated homogenous cell populations, the transplant model proved most useful. For long term analysis of effects of extraneous agents, the skin carcinogenesis model is probably the most rewarding. Analysis of proliferation markers in human tumor samples as studied by immunohistochemistry, showed that an increased expression of PCNA and Ki-67 was associated with poor prognosis in ovarian neoplasms. Analysis of cell proliferation in model tumors showed that the transplant model has a better sensitivity when compared to the animal skin model and the subcutaneous injection model, in that effect of changes in cell-host interaction on the location and extent of the proliferating cell population can be studied therein. The expression of some growth factors, their receptors, oncogenes and suppressor genes were studied in ovarian and endometrial carcinomas and in skin cancer model system in mouse exposed to carcinogens and UV irradiation. Variability in expression and methodological problems precluded detailed analysis of these markers in different models. The expression of TGFβ1, TGFβ2 and TGFβ3 was determined in normal human keratinocytes, and in 7 immortalized and ras-transfected benign and malignant keratinocyte cell lines, maintained as transplants and as subcutaneous tumors in nude mice. By differential immunohistochemical localization of TGFβ isoforms, we demonstrated that each isoform may serve specific roles in tumor development and progression. The complex nature of TGFβ expression prevented detailed analysis of isozymes in different models, the results in this study, however, indicated a similar pattern in the models analyzed. Morphological methods were used to determine relationship between epithelial growth and formation and deposition of collagens in the extracellular matrix in experimental models and human tumors. The composition of the mesenchyme differed in tumors originating from different cell lines reflecting functional interaction between epithelial cells and the mesenchyme in neoplastic development. Tumor-stroma interaction was distinct in human, comparable alterations were observed in experimental models, more so in transplants, less in subcutaneous tumors, affecting tumor growth and differentiation in the different models.

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Laitakari, J. (Jaakko). "Computer-assisted quantitative image analysis of cell proliferation, angiogenesis and stromal markers in experimental and laryngeal tumor development." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514269497.

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Abstract Automated quantitative computer-assisted morphometric analysis of immunohistochemical expression of markers of neoplastic development and progression in experimentally induced and in human neoplasms showed very high sensitivity and reproducibility, allowing analysis of large numbers of cell and tissue components. Totals of 26 million pixels, 25,000 cells and 1500 vessels were examined, with a sensitivity exceeding 99% and reproducibility exceeding 99%. The total expression of proliferating cell nuclear antigen (PCNA) and p53 increased consistently during 7H-dibenz[c, g] carbazole (DBC)-induced formation of dysplasias and squamous cell carcinomas (SCC:s) in hamster lung. In dysplasia, nuclear size and PCNA staining intensity increased; in SCC:s nuclear size decreased. In a retrospective study on archival material of human laryngeal squamous cell carcinomas, the occurrence and location of PCNA-positive cells were specifically related to the degree of differentiation. In SCC:s nuclear size decreased, while shape alterations and PCNA staining intensity increased in relation to degree of malignancy. In DBC-induced respiratory carcinogenesis increased collagen matrix synthesis occurred prior to neoplasm development. Among squamous cell carcinomas, in well-differentiated tumors, collagen deposition increased, as did fiber size, in moderately differentiated tumors collagen synthesis and the deposition of new collagen decreased. The increase in transforming growth factor beta expression in differentiated cells and in the matrix was isoform-specific. Increased angiogenesis in laryngeal tumor development occurred in preneoplastic states and in SCC: s, inversely related to the degree of differentiation. In well-differentiated neoplasms the vessels were lying in the direction of the BM, in moderately differentiated neoplasms vessels were lying in the direction of tumor invasion and in poorly differentiated neoplasms irregular, partly abnormal vessels intermixed with tumor cells. Small regular vessels predominated in benign conditions and large, irregular vessels in malignant conditions. Experimental models provided the advantage of examining homogenous, well-characterized neoplasm progression without interfering with the process. Morphometric methods provided detailed information on large numbers of cells, useful for studies of tumor behavior and with potential clinical applications.

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Traya, Gassan. "Efeito da obstrução biliar extra-hepática sobre translocação bacteriana, endotoxemia e fator de necrose tumoral alfa : estudo experimental em ratos." reponame:Repositório Institucional da UFPR, 1999. http://hdl.handle.net/1884/48638.

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Orientador: Clementino Zeni Neto
Co-orientador: João Carlos Domingues Repka
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde
Resumo: 0 objetivo do presente estudo foi avaliar o efeito da obstrução biliar extrahepática sobre a ocorrência de translocação bacteriana, endotoxemia e Fator de Necrose Tumoral a em ratos. Foram utilizados 60 ratos da linhagem Wistar, machos, divididos em seis grupos, com 10 ratos cada, a saber: grupo Controle, grupo Simulação, grupo 1D, grupo 2D, grupo 7D e grupo 14D. Os ratos do grupo Controle foram submetidos diretamente ao sacrifício, com coleta de sangue e órgãos, sem nenhum procedimento cirúrgico prévio. Os ratos do grupo Simulação foram submetidos a laparotomia com manipulação e simulação de ligadura do dueto biliar comum, 24 horas ante do sacrifício. Os ratos dos grupos 1D, 2D, 7D e 14D foram submetidos a ligadura do dueto biliar comum, com sacrifício após 1, 2, 7 e 14 dias respectivamente. Durante o sacrifício, foi coletado sangue por punção intracardíaca, para dosagens de bilirrubinas, endotoxinas, TNFa e para hemocultura. Em seguida, foram coletados swab de esfregaço de retroperitônio, rins, baço, fígado, pulmões e linfonodos mesentéricos para cultura, e fragmento de intestino delgado para contagem de bactérias. Cinco ratos morreram durante o experimento: 1 rato do grupo 2D, 1 rato do grupo 7D e 3 ratos do grupo Simulação Com relação às dosagens de endotoxinas e TNFa, todos os grupos com obstrução biliar extrahepática apresentaram níveis detectáveis., com aumento proporcional ao tempo de obstrução biliar extra-hepática. Ocorreu translocação bacteriana em 30% dos ratos do grupo 1D, 66,66% dos ratos do grupo 2D, 100% dos ratos dos grupos 7 e 14D e 28,57% dos ratos do grupo Simulação. Em relação ao número de bactérias translocadas, observou-se maior quantidade de bactérias nos grupos com maior tempo de obstrução biliar, sendo mais evidente no grupo 14D. Concluiu-se que obstrução biliar extra-hepática causa translocação bacteriana, endotoxemia e aumento dos níveis de TNFa circulantes. O aumento do tempo de obstrução biliar, cursa com aumento dos índices de translocação bacteriana, endotoxemia e TNFa circulantes.
Abstract: The aim of this study was to evaluate the effects of obstructive jaundice over the occurrence of bacterial translocation, endotoxemie and TNFa in a rat model. Sixty male Wistar rats were used, divided in 6 groups of 10 rats each, as follows: Control group, Sham ligated group, ID group, 2D group, 7D group and 14D group. Rats in the Control group were sacrificed for blood and tissue sampling only. In the Sham ligated group, a laparotomy was performed, with manipulation and sham ligation of the common bile ducts 24 hours prior to sacrifice. In groups ID, 2D, 7D and 14D, common bile ducts were ligated and the animals were sacrificed in 1 day, 2 days, 7 days and 14 days, respectively. During the sacrifice, blood was collected by intra-cardiac punch for bilirubins, endotoxins, TNFa measuring, and culture. After this, swabs of the retroperitoneal fluids, kidneys, spleen, liver, lungs and mesenteric limph node complex, were collected for culture, and fragment of small bowel was sent to bacterial count. Five rats died during the experiment. All rats with common bile ducts ligated had detectable levels of the endotoxins and TNFa, with proportional increase acquainted with obstruction time. Bacterial translocation occurred in 30% of the rats in the ID group, 66,66% of the rats in the 2D group, 100% of the rats in the 7D and 14D groups, and 28,57% of the rats in the sham operated group. The number of translocated bacterial was higher in the groups with higher time of the biliar obstruction. This was more evident in the 14D group. In conclusion, the extra-hepatic biliar obstruction causes bacterial translocation, endotoxemie and increase of seric levels of TNF. The increased time of biliar obstruction, leads to an even higher bacterial translocation rate, endotoxemie and seric levels of TNFa.

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Sá, Carla Sandrina Rendall Moreira. "Estudo da participação dos receptores do tipo Toll-2 e Toll-4 e da molécula adaptadora MyD88 no desenvolvimento do diabetes auto-imune experimental." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-18032014-151145/.

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O diabetes mellitus tipo 1 (DMT1) é uma doença autoimune caracterizada pela destruição das células b pancreáticas, por citocinas (IFN-g, IL-1b, e TNF-a) produzidas por macrófagos e linfócitos Th1. A participação de TLRs no desenvolvimento desta doença tem sido demonstrada, porém os mecanismos envolvidos são poucos elucidados. Neste trabalho avaliamos o papel de TLR-2, TLR-4 e molécula adaptadora MyD88 no desenvolvimento do DMT1 experimental induzido por múltiplas doses de estreptozotocina. Foi observada maior severidade do DMT1 em animais TLR-2 KO, elevada glicemia e acentuada perda de peso. Um maior infiltrado celular inflamatório, aumento da expressão de bax, caspase-3 e diminuição no número de ilhotas foram observados no grupo de animais TLR-2 KO. Interessantemente, uma diminuição significante na frequência de células T reguladoras foi verificada no baço dos animais TLR-2 KO diabéticos. A deficiência do TLR-2 resultou no desenvolvimento exacerbado do DMT1, sugerindo um importante papel dos TLR-2 na modulação da resposta imune desenvolvida nesta doença.
Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction by activated macrophages and Th1 lymphocytes. The role of TLRs has been demonstrated in this disease, however the mechanisms involved in this process have not yet been fully explained. We evaluated the role of TLR-2, TLR-4 and MyD88 adaptor molecule in the development of experimental autoimmune diabetes induced by multiple low-doses of streptozotocin in C57Bl/6 mice. TDM1 was more severe in TLR-2 KO mice, with higher blood glucose levels and weight loss. Increased cellular infiltrate, bax and caspase-3 expression was detected in the pancreatic islets of the diabetic TLR-2 KO group suggesting a greater destruction of pancreatic cells. Interestingly, a decreased number regulatory T cells was observed in the spleen of diabetic TLR-2 KO animals. Hence, TLR-2 receptor deficiency resulted in exacerbated development of experimental autoimmune diabetes, thereby suggesting an important role for this receptor in the modulation of the immune response developed in this disease.

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Assis, Frankcineia Aparecida de. "Efeito do selênio orgânico e da vitamina E no crescimento tumoral e na resposta imunológica ao tumor experimental de Ehrlich." Universidade Federal de Minas Gerais, 2007. http://hdl.handle.net/1843/ECJS-779NAN.

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Cancer incidence has increased all over the world; in Brazil this disease has been considered a public health issue. However, tumor establishment in the organism depends on the immunologic escape mechanism in which tumors cells have strategies to inhibit the immune system recognition. This escape mechanism contributes to the tumor growth and development, so the tumor can invade the organism being able to cause serious damages or even death to the host if it is not treated in time. The number of researches has also increased intending to find out the healing or, at least a better quality of life for those individuals that suffer from cancer. One of the actual researches line refers to the usage of antioxidant for treating or preventing cancer. Between the composts utilized are the selenium and vitamin E. In this work, we studied the effect of organic selenium and vitamin E in Ehrlich tumors (solid form) growth and immunologic answer to this tumor. Eight weeks old females mice BALB/c, split up into 6 groups were given the following diet: selenium supplemented diet, vitamin E supplemented diet and non supplemented diet. After two weeks treatment three groups received 2,5x106 tumor cells by footpad and other 3 groups received saline 0,9%. These animals were kept in diet for four weeks thereafter, then they were sacrificed and spleen, lymph nodes popliteal, footpad and blood were collected. Our results show that only those animals supplemented with vitamin E presented a tumor growth inhibition. These animals also had a higher CD69 expression by NK cells and CD8+ lymphocytes in the lymph nodes popliteal what reflects a higher activation of these cells. Furthermore, the animals supplemented with vitamin E without tumor inoculation showed a higher percentage of NK cells in the lymph nodes popliteal and spleen, the same result was seen in spleen from animals supplemented with selenium without tumor inoculation. The vitamin E treatment also reduced the percentage of CD4+CD25+ cells in the spleen and inhibited IL-10 production by lymph nodes popliteal cells and NO production by spleen cells. Histology showed that both treatments have the same characteristic, with the same size and mononuclear infiltrated necrosis areas. However, apoptosis rate analyses in the tumor footpad histology showed that animals treated with vitamin E presented a higher apoptosis rate when compared with other groups. The results from our study showed that vitamin E supplementation is able to inhibit Ehrilch tumors growth, activating immune system cells such as NK lymphocytes that culminate in apoptosis induction of tumors cells.
O câncer tem aumentado em todo o mundo, e no Brasil essa doença é colocada como problema de saúde pública pelos órgãos responsáveis. Contudo, o estabelecimento do tumor no organismo depende do mecanismo de escape imunológico, no qual as células tumorais possuem estratégias para inibir o seu reconhecimento pelo sistema imune. Esse escape contribui com o crescimento e desenvolvimento do tumor, que evade o organismo, podendo causar danos graves e até mesmo a morte do indivíduo se não tratado em tempo hábil. Tem aumentado também pesquisas no intuito de descobrir a cura e melhorar a qualidade de vida de indivíduos portadores de câncer. Uma das linhas atuais de pesquisa refere-se a uso de antioxidantes na prevenção ou no tratamento do câncer. Entre os compostos mais estudados estão o selênio e a vitamina E. Neste trabalho, nós analisamos o efeito do selênio orgânico e da vitamina E no crescimento e na resposta imunológica ao tumor de Ehrlich na forma sólida. Camundongos fêmeas BALB/c de 8 semanas de idade separados em 6 grupos receberam as seguintes dietas: dieta sem suplementação, dieta suplementada com selênio e dieta suplementada com vitamina E. Após duas semanas de tratamento 3 grupos receberam 2,5 x106 células de tumor no coxim plantar esquerdo e os outros 3 grupos receberam salina a 0,9%. Esses animais permaneceram na dieta por mais 4 semanas, quando foram sacrificados e tiveram o baço, o linfonodo poplíteo, o coxim plantar, o sangue total e o soro coletados. Nossos resultados mostram que somente os animais suplementados com vitamina E e inoculados com tumor tiveram inibição no crescimento tumoral. Esses animais também apresentaram uma maior expressão de CD69 por células NK e linfócitos TCD8+ no linfonodo poplíteo, que reflete uma maior ativação dessas células. Além disso, os animais suplementados com vitamina E sem inoculação tumoral apresentaram um maior percentual de células NK no linfonodo poplíteo e no baço, o mesmo resultado foi visto no baço de animais suplementados com selênio e sem inoculação tumoral. O tratamento com vitamina E também reduziu o percentual de células CD4+CD25+ no baço, além de inibir a produção de IL-10 por células do linfonodo poplíteo e NO por células do baço. A histologia mostrou que ambos os tratamentos possuem a mesma característica, com área de necrose de mesmo tamanho e infiltrado característico de mononuclear. Contudo, a análise do índice de apoptose no corte histológico do coxim plantar com tumor mostrou que, os animais suplementados com vitamina E apresentaram um maior índice quando comparados aos demais grupos. Nossos resultados mostram que a suplementação com vitamina E é capaz de inibir o crescimento do tumor de Ehrlich, ativar células do sistema imunológico como e células NK, culminando na indução de apoptose das células tumorais.

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Lopardo-Spehner, Véronique. "Stress et immunomodulation : modulation de l'activation des macrophages murins apres stress experimental et role de l'immunomodulation therapeutique." Besançon, 1996. http://www.theses.fr/1996BESA3703.

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Åström, Maria. "Prognosis in acute myeloid leukemia and influence of monocytic markers : epidemiological, clinical and experimental studies /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-512-3/.

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Mangueira, Vivianne Mendes. "Estudo da toxicidade e atividade antitumoral do derivado acridínico n’-(2-cloro-6-metoxi-acridin-9-yl)-2-ciano-3-(4-dimetilaminofenil)-acrilohidrazida em modelo experimental de tumor ascítico de ehrlich." Universidade Federal da Paraíba, 2015. http://tede.biblioteca.ufpb.br:8080/handle/tede/8821.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Cancer is a major public health problem worldwide and is considered a group of diseases characterized by uncontrolled growth and multiplication of abnormal cells that can invade various tissues. Treatment has been benefited from research that seek to reduce toxicity and increase the effectiveness of different anticancer drugs. Acridine derivatives have a number of proven biological activities, and amsacrine, an antineoplastic used for the treatment of leukemias and lymphomas, is the main representative of the group. This study aimed to evaluate the toxicity and antitumor activity of acridine- derived N’-(2-chloro-6-methoxy-acridin-9-yl)-2-cyano-3-(4-dimethylaminophenyl)-acrilohydrazide (ACS-AZ10). In the assessment of cytotoxicity in mouse erythrocytes it was observed that ACS-AZ10 did not cause hemolysis at the concentrations tested (up to 1250 μg / ml), suggesting low toxicity in erythrocytes. After acute administration of ACS-AZ10 (2000 mg / kg) in mice intraperitoneally (ip), characteristic effects of changes in the central nervous system among them, writhing and abduction of the legs of the rear train, were observed. The estimated LD50 (dose that produces death in 50% of experimental animals) was around 2500 mg / kg. The ACS-AZ10 (15 or 30 mg / kg), after a nine days treatment (ip) showed significant antitumor activity in vivo in Ehrlich ascites carcinoma model (EAC), considering the volume parameters, mass, viability and total cell count. Treatment at the dose 7.5 mg/kg induced an increase in sub-G1 peak, with a consequent reduction in the percentage of cells in G0/G1 and S phases of cell cycle, suggesting death by apoptosis. However, treatment with 15 mg/kg induced cell cycle arrest in G2/M phase and a reduction of the fraction G0/G1 and S, suggesting a pre-mitotic blockade. The treatment with different doses of ACS-AZ10 significantly reduced the angiogenic capacity of the EAC, thus it can be inferred that the ACS-AZ10´s antitumor mechanism of action involves, at least in part, an anti-angiogenic effect. The toxicological analysis indicated that after nine days of treatment with ACS-AZ10, low haematological and biochemical toxicity were observed. Histopathological analysis indicated liver damage following treatment with ACS-AZ10, however, the damage was considered mild and reversible. ACS-AZ10 induced no increase in the quantity of micronucleated erythrocyte in micronucleus test, indicating the absence of genotoxic under the conditions evaluated. Therefore, it is possible to infer that the ACS-AZ10 has potent antitumor activity in vivo with low toxicity.
O câncer é um importante problema de saúde pública em nível mundial, sendo considerado um grupo de doenças caracterizadas pelo crescimento descontrolado e multiplicação de células modificadas que podem invadir diversos tecidos. Seu tratamento tem se beneficiado das pesquisas que buscam reduzir a toxicidade e aumentar a eficácia de diferentes fármacos antineoplásicos. Os derivados da acridina possuem diversas atividades biológicas comprovadas, sendo a amsacrina, um antineoplásico usado para o tratamento de leucemias e linfomas, o principal representante do grupo. Esse trabalho teve como objetivo avaliar a toxicidade e atividade antitumoral do derivado acridínico N’-(2-cloro-6-metoxi-acridin-9-yl)-2-ciano-3-(4-dimetilaminofenil)-acrilohidrazida (ACS-AZ10). Na avaliação da citotoxicidade em eritrócitos de camundongos foi possível observar que o ACS-AZ10 em concentração de até 1250 g/mL não causou dano direto a membrana de eritrócitos de camundongos, sugerindo atividade intracelular em hemácias. Após administração aguda do ACS-AZ10 (2000 mg/kg) em camundongos por via intraperitoneal (i.p.), foram observados efeitos característicos de alterações no Sistema Nervoso Central dentre estes, contorções abdominais e abdução das patas do trem posterior. O valor estimado da DL50 (dose que produz morte de 50% dos animais experimentais) foi em torno de 2500 mg/kg. O ACS-AZ10 (15 ou 30 mg/kg), após nove dias de tratamento (i.p.), mostrou significante atividade antitumoral in vivo em modelo de Carcinoma Ascítico de Ehrlich (CAE), considerando os parâmetros volume, massa, viabilidade e total celular. O tratamento na dose 7,5 mg/kg induziu um aumento do pico sub-G1, com consequente redução da percentagem de células nas fases G0/G1 e S do ciclo celular, o que sugere morte por apoptose. No entanto, o tratamento com a dose de 15 mg/kg induziu parada do ciclo celular na fase G2/M e diminuição da fração G0/G1 e S, o que sugere um bloqueio pré-mitótico. O tratamento com as diferentes doses de ACS-AZ10 diminuiu significativamente a capacidade angiogênica do CAE, desta forma, pode-se inferir que o mecanismo de ação antitumoral do ACS-AZ10 envolve, pelo menos parcialmente, um efeito antiangiogênico. As análises toxicológicas indicaram que, após nove dias de tratamento com ACS-AZ10 foi observada baixa toxicidade hematológica e bioquímica. A análise histopatológica indicou danos hepáticos após o tratamento com ACS-AZ10, entretanto, os danos foram considerados leves e reversíveis. O ACS-AZ10 não induziu aumento na quantidade de eritrócitos micronucleados no ensaio do micronúcleo, o que indica ausência de genotoxicidade, nas condições avaliadas. Portanto, é possível inferir que o ACS-AZ10 apresenta potente atividade antitumoral in vivo com baixa toxicidade.

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PUJATTI, PRISCILLA B. "Desenvolvimento de derivados da bombesina radiomarcados com lutecio-177: relacao estrutural e potencial diagnostico-terapeutico para tumor de prostata." reponame:Repositório Institucional do IPEN, 2009. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9489.

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Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

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Pandit, Bulbul. "Study of structure activity relationship of analogs derived from SU-5416 and thalidomide and mechanism of antiproliferative activity." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187127289.

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Medrano, Ruan Felipe Vieira. "Remediação das vias p53/Arf e interferon-beta como uma estratégia de imunoterapia do câncer: uma abordagem de transferência gênica." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-06042018-122815/.

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As células tumorais prosperam como consequência da capacidade de resistir aos mecanismos de morte celular e de evasão da vigilância imunológica. Nós propomos que, em cânceres que possuem o supressor de tumor p53 selvagem, a remediação de ambas dessas defesas pode ser promovida pela transferência genica combinada de vetores adenovirais portadores dos transgenes de p19Arf (proteína supressora de tumor, parceira funcional de p53) e de interferon-beta (IFNbeta, citocina imunomoduladora). De fato, em resultados anteriores, notamos que a transdução combinada (p19Arf/IFNbeta), mas não os tratamentos individuais, em células de melanoma murino B16F10 resulta em aumento massivo de morte celular. Porém a capacidade destas células em processo de morte de desencadear imunidade antitumoral não foi analisada. Nesta tese e em estudos complementares, buscamos investigar os mecanismos moleculares de morte celular envolvidos na resposta imune estimulada por p19Arf/IFNbeta e explorar sua aplicação como imunoterapia do câncer. Inicialmente, em modelo de vacinação profilática, revelamos que o tratamento combinado em células B16F10 promove a expressão de IL-15, ULBP1, dos receptores de morte FAS/APO1 e KILLER/DR5, assim como uma resposta de células natural killer que rejeitam estas células tratadas quando inoculadas em camundongos imunocompetentes singênicos. Após desafio tumoral no flanco oposto, a progressão desses tumores foi fortemente reduzida devido ao engajamento de linfócitos T CD4+ e CD8+, que apresentaram produção aumentada das citocinas IFN-? e TNF-alfa e medeiam proteção antitumoral de longo prazo. Em seguida, explorando um contexto de imunização diferente, a transferência de gênica in situ foi realizada em carcinoma heterotópico de pulmão e exibiu proteção significativa contra um desafio tumoral secundário, apenas quando o tumor primário foi tratado com p19Arf/IFNbeta. Análise de transcriptoma destes tumores indicou uma assinatura quimiotáxica de neutrófilos e linfócitos T CD8+ através das quimiocinas CCL3, CXCL3 e da IL-1beta. Em apoio destas observações, análises mecanicistas in vitro revelaram que células tratadas com p19Arf/IFNbeta ativam programas apoptóticos de p53 e antivirais de IFNbeta, enquanto sucumbem a um processo de morte por necroptose que também libera moléculas de morte celular imunogênica (MCI), calreticulina, ATP e HMGB1. No entanto, procurando potencializar ainda mais o benefício terapêutico dos nossos vetores, exploramos sua associação com o quimioterápico imunogênico doxorrubicina (Dox), que também é indutor de MCI. E nesta associação, percebemos que a Dox aumenta não apenas os níveis de morte celular, mas também a imunogenicidade das células tratadas, proporcionando em um modelo de vacina terapêutica, um controle tumoral superior em camundongos que já portavam antes da vacinação tumores B16F10 ou MCA205. Além disso, a associação in situ destas terapias restaurou a eficácia de uma dose sub-terapêutica de Dox, que em contraste com sua dose terapêutica, não prejudica a função cardíaca. Finalmente, também exploramos a associação com o bloqueio dos pontos de controle imunológicos PD-1 ou CTLA-4, que no modelo de vacina terapêutica, sua associação induziu maior rejeição completa de tumores B16F10. Em conclusão, aqui apresentamos evidências sobre a capacidade da combinação p19Arf/IFNbeta de induzir morte celular e estimulação imunológica. E ressaltamos seu potencial como uma estratégia de imunoterapia do câncer
Cancer cells thrive as a consequence of resisting cell death mechanisms and escaping from immune surveillance. We propose that, in cancers that harbor the wild-type tumor suppressor p53, remediation of both of these defenses can be achieved by harnessing the adenoviral vector mediated gene transfer of p19Arf (tumor suppressor protein, p53 functional partner) together with interferon-beta (IFNbeta, immunomodulatory cytokine). Indeed, in our initial observations, it was noticed that combined-transduction (p19Arf/IFNbeta), but not the individual treatments, of B16F10 mouse melanoma cells results in massive cell death levels. Yet, the capability of these dying cells to unleash antitumor immunity was not investigated. Here in this thesis and in complementary studies, we sought to investigate the molecular mechanisms of cell death involved in the p19Arf/IFNbeta immune stimulation and explore its potential as a mediator of cancer immunotherapy. First, in a prophylactic B16F10 vaccine model, we revealed that the dual treatment led to the up-regulation of IL-15, ULBP1, FAS/APO1 and KILLER/DR5 death receptors, plus a natural killer cell response that completely rejects treated cells when inoculated in syngeneic immunocompetent mice. Whereas, upon a contralateral tumor challenge, progression was strongly reduced by engaging both CD4+ and CD8+ T cells, which displayed augmented production of IFN-? and TNF-alpha cytokines and provided long term antitumor protection. Next, exploring different immunization context, in situ gene transfer in a heterotopic lung carcinoma exhibited significant protection against a secondary tumor challenge only when the primary tumor was treated with p19Arf/IFNbeta. Transcriptome analysis of these treated tumors indicated a chemotaxic signature of neutrophils and CD8+ T cells with the involvement of CCL3, CXCL3 chemokines and IL-1beta. Moreover, in support of this evidence, mechanistic in vitro studies revealed that p19Arf/IFNbeta treated cells reactivate p53 apoptotic and IFNbeta antiviral programs, while succumbing to a necroptosis cell death processes that also releases immunogenic cell death (ICD) molecules, calreticulin, ATP and HMGB1. Yet, aiming to potentiate therapeutic benefit of our vectors, we explored their association with doxorubicin (Dox) immunogenic chemotherapy, which is also an inducer of ICD. And in this setting, this association with Dox enhances not only cell death levels but also immunogenicity of treated cells, providing superior tumor control in a therapeutic vaccine model, where mice were already bearing B16F10 tumors or MCA205 sarcomas before vaccination. Moreover, associated use of these therapies in situ rescued efficacy of a sub-therapeutic dose of Dox, which in contrast to its therapeutic dose, does not impair cardiac function. Finally, we also evaluated the association with PD-1 or CTLA-4 checkpoint blockade immunotherapy, which in the therapeutic vaccine model induced full tumor rejection in a greater number of mice. In sum, here we provide compelling evidence for the ability of the p19Arf/IFNbeta combined gene transfer to promote cell death and immunogenic stimuli and underscored its potential to be applied as a cancer immunotherapy strategy

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Tiar, Feriel. "Développement d'un nouveau modèle orthotopique de glioblastome humain chez la souris." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENV078.

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Le glioblastome représente le sous-type de tumeur cérébrale le plus fréquent et le plus agressif. Malgré une meilleure compréhension de la maladie ainsi que l'émergence de nouvelles cibles, voire de nouveaux outils thérapeutiques, son pronostic reste inchangé. En effet, l'échec de l'extrapolation des résultats vers la clinique met en exergue la nature complexe de la maladie et la dimension décisive des modèles animaux adéquats et prédictifs dans l'étude des nouvelles thérapies. Et pour cause, un modèle animal idéal doit pouvoir reproduire les caractéristiques histo-pahologiques, génétiques et diagnostics de la pathologie humaine. Il doit avoir également une survie suffisante pour permettre la mise en place et l'évaluation de nouveaux traitements. Au cours de ce travail, nous avons développé un nouveau modèle de tumeur orthotopique chez la souris à partir de cellules de glioblastome humain cultivées en neurosphères. D'une façon similaire aux protocoles cliniques de neuro-imagerie, les techniques classiques d'IRM et les critères radiographiques ont été utilisés afin d'étudier la croissance tumorale de ce modèle ainsi que l'évaluation de sa réponse au traitement à base de temozolomide. Les observations par imagerie ont été complétées et/ou confirmées par examen histologique ainsi que par l'étude du transcriptome. Comme en clinique, ce nouveau modèle orthotopique présente une tumeur invasive et nécrotique, une résistance au temozolomide ainsi que des signatures moléculaires associées aux observations histologiques. De plus, ce modèle tumoral est caractérisé par une dynamique de signalisation promouvant l'invasion, la migration et la résistance à l'apoptose à l'origine de sa survie post-thérapeutique. Ainsi, ce modèle préclinique mime, au plus près, les caractéristiques de la pathologie humaine avec une médiane de survie des animaux de 82 jours, ce qui le rend pertinent pour l'évaluation préclinique des nouvelles stratégies thérapeutiques
Glioblastoma is the most common and aggressive subtype of brain tumors. Despite a better understanding of the disease and also the emergence of new therapeutic targets and strategies, the prognosis of patients remains unchanged. The failure to extrapolate preclinical results to the clinics highlights the complex nature of the disease and the importance of appropriate and predictive animal models for the study of new therapies. A pertinent animal model should be able to reproduce the characteristic of the human pathology in terms of disease development pattern, histological and transcriptomic specification, drug failure as well as diagnostic features. In this work, we developed a novel orthotopic mouse model derived from human glioblastoma spheres. Like in clinics, conventional MRI techniques and radiographic criteria were used to characterize tumor growth and treatment response to temozolomide. MRI findings have been completed and/or confirmed by histological examination and transcriptomic studies. Like clinically encountered tumors, this new orthotopic tumor model presents an infiltrating growth pattern, resistance to temozolomide and a molecular signature associated with histological features. In addition, this tumor model is characterized by a dynamic signaling pathway, which promotes cell invasion and migration as well as resistance to apoptosis and consequently to treatment. Thus, this preclinical model mimics clinical features of human glioblastoma and has a median host survival time of 82 days, which would be relevant in the assessment of preclinical therapies

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48

Galliher, Amy Jo. "[Beta]₃ integrins enhance TGF-[beta]-mediated tumor progression in mammary epithelial cells /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

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Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2007.
Typescript. Non-Latin script record Includes bibliographical references (leaves 112-128). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

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Guzovsky, Eric Marcel. "Análise de alterações histopatológicas e celulares em tecidos de camundongos C57BL/6J inoculados com células de melanoma experimental B16F10 por via subcultanea e tratados com o imunomodulador Imiquimod 5%." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-30052012-092333/.

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Imiquimod é uma imidazoquinolina, agonista do TLR-7, ativador de células dendríticas (DC) e indutor da transcrição de diversas citocinas. O objetivo deste estudo é avaliar o crescimento tumoral, a formação de metástases em órgãos internos, a atividade do sistema imune e o tipo de morte celular induzido devido ao tratamento tópico. Camundongos foram inoculados com células de melanoma murino B16F10. O fármaco, na dose de 5mg, foi aplicado no local da inoculação uma vez por dia até o fim do experimento. Foram estudados quatro grupos experimentais, dois inoculado com células tumorais, sendo um tratado e outro não, e outros dois grupos, um recebeu somente o tratamento com o fármaco e o outro não recebeu tratamento. Os animais foram pesados e seus tumores medidos periodicamente. Exemplares dos grupos foram sacrificados em quatro tempos diferentes, imediatamente submetidos à necropsia para a análise de massas tumorais por citometria de fluxo com caspase-3 e anexina-v para investigar a indução de apoptose e/ ou necrose tumoral, e remoção do tumor, pele, Baço, linfonodo e pulmão, que foram fixados, inclusos em parafina, cortados e corados com HE, para análise histológica.
Imiquimod is a TLR-7 agonist and activator of dendritic cells (DC), and induces transcription of several cytokines. This study`s objective is to evaluate tumor growth, development of metastasis within internal organs and the immune system`s function, due to the topical treatment. Two groups of C57BL/6J mice were inoculated with B16F10 melanoma cells subcutaneously, and only one of the groups was treated, applied topically at the injection site once a day, followed by a second round of two groups, one treated and the other as a healthy group. Every two tumors and weight were measured. In order to observe the tumor progression and treatment effects, groups of animals were sacrificed on four days apart and immediately submitted to necropsy for a tumor analysis by flow cytometry, to evaluate the induction of apoptosis and necrosis, and to macroscopically observe the tumor development within internal organs, vascularization and posterior inclusion of the organs in paraffin for histological analysis. Tumor, skin, spleen, limph node and lung were colored with HE for histological analysis of migrating immune system cells and tumoral cells in the organs and describing its integrity.

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Furrer, Markus Kurt. "Isolated cytostatic lung perfusion : experimental assessment of different modalities and study of antitumor activity of human recombinant tumor necrosis factor-alpha /." [S.l : s.n.], 1998. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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Dissertations / Theses on the topic 'Experimental tumor'

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