Monocarboxylate transporters (MCTs) have been shown to be important in regulating metabolism during hypoxia in mammals. However, the role of MCTs in hypoxic survival in lower vertebrates is currently unclear. The goal of this study was to investigate the coordination of MCTs along with other metabolic proteins during hypoxia. Therefore, we subjected zebrafish (Danio rerio) to 1.5 mg L-1 O2 over 48 and 96-hr and measured tissue-specific transcriptional changes of MCTs (1, 2 and 4), lactate dehydrogenase A (LDHa), citrate synthase (CS), and other metabolic proteins using real-time RT-PCR. There were no changes in mRNA in muscle at 48 and 96-hr. When data from both time points were pooled in brain, a significant increase was found in MCT4 (+102%) and LDHa (+28%) mRNA indicating a preference towards glycolysis. In gills, there were increases in LDHa at 48-hr (+101%) and MCT1 (+24%) mRNA from pooled data suggesting that both anaerobic and aerobic metabolism is being utilized. Heart had the greatest changes in transcriptional levels compared to other tissues. At 48-hr, increases were found in MCT1 (+117%), MCT4 (+86%), LDHa (+197%), and pooled data showed an increase in CS (+18%) mRNA. These results indicate that the influx and efflux of lactate are both employed as strategies in cardiac tissue during hypoxia. This study has shown that fish utilize tissue-specific regulation of MCTs along with other metabolic genes during hypoxia. / Thesis (Master, Biology) -- Queen's University, 2009-08-24 13:44:06.114

No description available.

O trabalho aqui apresentado é resultado de uma pesquisa onde se procurou caracterizar os solos da Região Metropolitana de Fortaleza (RMF). Inicialmente, o objetivo deixou de ser principal devido às limitações desse método quando aplicado aos solos da RMF. O objetivo principal do trabalho passou a ser estudar mais detalhadamente os solos que ocorrem na Região Metropolitana de Fortaleza à luz de métodos convencionais e não convencionais, para aplicação na engenharia rodoviária. Para tanto, foram estudados sessenta solos pertencentes às classes pedológicas que ocorrem na RMF. Esses solos foram submetidos a um programa experimental que envolveu a execução de ensaios \"convencionais\" e \"não convencionais\". A partir dos resultados experimentais foram estabelecidas correlações entre os valores de algumas propriedades de interesse à pavimentação realizadas em cilindro convencional e miniatura. Tentou-se determinar o valor de CBR de um solo, dispondo das cargas calculadas no ensaio mini-CBR, mas essa tarefa não logrou êxito. As amostras foram classificadas pelas classificações HBR e MCT para verificação da qualidade da previsão das propriedades dos solos obtidas por esses métodos e aqueles resultantes da execução dos ensaios de laboratório. Foi proposto, a partir da execução de ensaio de adsorção de azul de metileno, a inclusão no ábaco de três zonas para se caracterizar o comportamento dos solos da RMF. Os resultados experimentais permitiram, também, concluir que pode-se identificar os materiais com potencial de uso na pavimentação de sua classe pedológica. / The work here presented is resulted of an experimental research where tried to characterize the soils of the Fortaleza Metropolitan Area (FMA). Initially, the thesis original objective was to transpose the MCT method to the reality of the occurrence soils in FMA. This objective quit being main due to the limitations of that method when applied to the FMA soils. The main objective of the work became to study the soils that occur in Fortaleza Metropolitan Area to the light of conventional methods in full detail and not usual, to know their limitations and real potentialities better for application in the road engineering. For so, sixty soils belonging to the pedological classes that occur in FMA were studied. These soils were submitted to an experimental program that involved the execution of \"conventional\" and \"not usual\" tests. Starting from the experimental results correlations among some properties values of paving interest accomplished in conventional cylinder and miniature were established. Tried to determine the CBR soil value, having the estimated loads in the mini-CBR test, but this task didn\'t achieve success. The samples were classified by the HRB and MCT classifications to verificate the quality of the forecast of the soils properties obtained by those methods and those execution resultants of the tests laboratory. It was proposed, starting from the execution of methylene blue adsortion test, the inclusion in the activity abacus of three areas to characterize the behavior of the FMA soils. The experimental results allowed also concluding that are possible to identify materials that have potential pavements use through their pedological class.

O trabalho aqui apresentado é resultado de uma pesquisa onde se procurou caracterizar os solos da Região Metropolitana de Fortaleza (RMF). Inicialmente, o objetivo deixou de ser principal devido às limitações desse método quando aplicado aos solos da RMF. O objetivo principal do trabalho passou a ser estudar mais detalhadamente os solos que ocorrem na Região Metropolitana de Fortaleza à luz de métodos convencionais e não convencionais, para aplicação na engenharia rodoviária. Para tanto, foram estudados sessenta solos pertencentes às classes pedológicas que ocorrem na RMF. Esses solos foram submetidos a um programa experimental que envolveu a execução de ensaios \"convencionais\" e \"não convencionais\". A partir dos resultados experimentais foram estabelecidas correlações entre os valores de algumas propriedades de interesse à pavimentação realizadas em cilindro convencional e miniatura. Tentou-se determinar o valor de CBR de um solo, dispondo das cargas calculadas no ensaio mini-CBR, mas essa tarefa não logrou êxito. As amostras foram classificadas pelas classificações HBR e MCT para verificação da qualidade da previsão das propriedades dos solos obtidas por esses métodos e aqueles resultantes da execução dos ensaios de laboratório. Foi proposto, a partir da execução de ensaio de adsorção de azul de metileno, a inclusão no ábaco de três zonas para se caracterizar o comportamento dos solos da RMF. Os resultados experimentais permitiram, também, concluir que pode-se identificar os materiais com potencial de uso na pavimentação de sua classe pedológica. / The work here presented is resulted of an experimental research where tried to characterize the soils of the Fortaleza Metropolitan Area (FMA). Initially, the thesis original objective was to transpose the MCT method to the reality of the occurrence soils in FMA. This objective quit being main due to the limitations of that method when applied to the FMA soils. The main objective of the work became to study the soils that occur in Fortaleza Metropolitan Area to the light of conventional methods in full detail and not usual, to know their limitations and real potentialities better for application in the road engineering. For so, sixty soils belonging to the pedological classes that occur in FMA were studied. These soils were submitted to an experimental program that involved the execution of \"conventional\" and \"not usual\" tests. Starting from the experimental results correlations among some properties values of paving interest accomplished in conventional cylinder and miniature were established. Tried to determine the CBR soil value, having the estimated loads in the mini-CBR test, but this task didn\'t achieve success. The samples were classified by the HRB and MCT classifications to verificate the quality of the forecast of the soils properties obtained by those methods and those execution resultants of the tests laboratory. It was proposed, starting from the execution of methylene blue adsortion test, the inclusion in the activity abacus of three areas to characterize the behavior of the FMA soils. The experimental results allowed also concluding that are possible to identify materials that have potential pavements use through their pedological class.

Le lactate est considéré comme un métabolite déchet depuis de très nombreuses années. Cependant, cette vision semble revisitée depuis quelques temps, avec l'apparition de la notion de glycolyse aérobie et de navettes lactate dans différents types cellulaires (muscle, cerveau et sperme). Concernant le cerveau, des études in vitro, ex vivo et in vivo réalisées ces 20 dernières années ont montré, d'une part, que les astrocytes produisent du lactate et d’autre part que le lactate pouvait être un substrat énergétique pour le système nerveux central (SNC), et plus particulièrement les neurones. Cette notion de navette lactate entre astrocyte et neurone a été proposée pour la première fois en 1994 par Pellerin et Magistretti (ANLS, pour astrocyte-neuron lactate shuttle). Malgré de nombreuses recherches depuis, l'existence d'un transfert net de lactate entre les astrocytes et les neurones n'a toujours pas pu être démontrée in vivo. Dans cet optique, la visualisation de la production de lactate in vivo dans le cerveau activé est essentielle. Le rôle des transporteurs au lactate, MCTs (Monocarboxylate Transporters), dans la détection de ce signal est également un point capital. L’objectif de cette thèse a été de développer la spectroscopie de RMN in vivo localisée dans le cortex somato-sensoriel du rat en condition d’activation cérébrale. Dans un premier temps, un travail de développement a été effectué afin de mettre au point le protocole de stimulation neuronale et d’obtenir un rapport signal sur bruit suffisant pour pouvoir quantifier de façon fiable le lactate. Une fois le protocole établi sur des rats contrôles, l’étude a été réalisée sur des rats modifiés génétiquement et réprimés pour le MCT, soit neuronal, soit astrocytaire. Le but était de déterminer si ce partenaire clef de l’ANLS avait une influence sur les fluctuations de lactate lors de l'activation cérébrale. En plus de la spectroscopie proton in vivo et de l’IRM fonctionnelle, des études de RMN du carbone-13 ont été réalisées ex vivo. Le résultat majeur de cette thèse montre qu’en l’absence du transporteur de lactate neuronal, non seulement on perd l’augmentation de lactate lors de la stimulation cérébrale mais on perd également le signal BOLD sur l’IRMf. Ce résultat suggère, et ce pour la première fois, que l’activité neuronale est fortement dépendante du transporteur au lactate. / Lactate has been considered as a waste metabolite for many years. However, this vision has been reconsidered recently, with the appearance of the notion of aerobic glycolysis and lactate shuttles in different cell types (muscle, brain, and sperm). Concerning the brain, in vitro, ex vivo and in vivo studies carried out over the last 20 years have shown, on the one hand, that astrocytes produce lactate and, on the other hand, that lactate can be an energetic substrate for the central nervous system (CNS), and more particularly neurons. This lactate shuttle between astrocyte and neuron was first proposed in 1994 by Pellerin and Magistretti (called ANLS, for astrocyte-neuron lactate shuttle). Despite many studies since then, the existence of a net transfer of lactate between astrocytes and neurons has still not been demonstrated in vivo. In this regard, visualization of lactate production in vivo in the activated brain is essential. The role of lactate transporters, MCTs (Monocarboxylate Transporters), in detecting this signal is also a key issue. The objective of this thesis was to develop in vivo NMR spectroscopy located in the somato-sensory cortex of rats under brain activation conditions. First, experiments were carried out to develop the neural stimulation protocol and to obtain a sufficient signal-to-noise ratio to be able to quantify lactate. Once the protocol was established on control rats, the study was performed on genetically modified rats and down-regulated for MCT, either neuronal or astrocytic. The aim was to determine whether this key partner of the ANLS has an influence on lactate fluctuations during brain activation. In addition to in vivo proton spectroscopy and functional MRI, carbon-13 NMR studies were performed ex vivo. The major result of this thesis shows that in the absence of the neuronal lactate transporter, not only is the increase in lactate lost during brain stimulation but the BOLD signal on the fMRI is also lost. This result suggests, for the first time, that neural activity is highly dependent on the lactate transporter.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This research aimed to classify soils from the region of Santa Maria, in the state of Rio Grande do Sul, according to the MCT Methodology, seeking to know the peculiarities of the tropical soils of the region. The methodology applied in this study consisted in situate, collect and characterization of the soil deposits, and the conduction of laboratory tests. It was chosen two typical soil profiles from the geotechnical units of the region and two materials from deposits inside the studied area. Through laboratory tests, materials were classified according to the traditional systems of geotechnical classification, USCS and TRB, which are based in regulations from United States and Europe, temperate climate regions, and are substantiated in the value of consistence limit and soil granulometry. Besides the physical, chemical and mechanical characterization, it was performed triaxial tests with repeated loads to obtain the resilience modulus and resilient classification of the studied soils. The experiments of the MCT, MCT-M and Tablets Method were performed to understand the behavior of the soils, in view of the subtropical climate in the state and the presence of lateritic soils. Thus, it is possible to compare the classification methods, verifying the deficiency in the traditional methods related to lateritic soils and prove the validity of the Tablets Method as a simplified form to soils characterization. The results of this research show that MCT Methodology, developed to tropical soils, is an important tool to make feasible projects of low traffic pavements, minimizing costs and optimizing the use of tropical soils in these enterprises. / Esta pesquisa teve como objetivo classificar os solos da região de Santa Maria, no estado do Rio Grande do Sul, segundo a metodologia MCT, objetivando conhecer as peculiares dos solos tropicais da região. A metodologia aplicada neste trabalho consistiu na localização, coleta e caracterização das jazidas de solos, e na realização de ensaios laboratoriais. Escolheram-se dois perfis típicos de solos das unidades geotécnicas da região e dois materiais provenientes de jazidas compreendidas na área de estudo. Através de ensaios laboratoriais, os materiais foram classificados segundo os sistemas tradicionais de classificação geotécnica, USCS e TRB, os quais são baseados em normativas dos Estados Unidos e Europa, regiões de clima temperado, e fundamentam-se nos valores de limites de consistência e na granulometria dos solos. Além da caracterização física, química e mecânica, foram realizados ensaios triaxiais de cargas repetidas para obtenção do módulo de resiliência e classificação resiliente dos solos em estudo. Os ensaios da classificação MCT, MCT-M e o Método das Pastilhas foram realizados para o conhecimento do comportamento dos solos, tendo em vista o clima subtropical do estado e a presença de solos lateríticos. Possibilitando assim, a comparação entre os métodos de classificação, verificando a deficiência nos métodos tradicionais em se tratando de solos lateríticos e a validade do Método das Pastilhas como uma forma simplificada de caracterização dos solos. Os resultados desta pesquisa mostram que a metodologia MCT, desenvolvida para solos tropicais, é uma ferramenta importante para viabilizar projetos de pavimentação de baixo volume de tráfego, minimizando custos e otimizando o uso de solos tropicais nesses empreendimentos.

Introduction : Un hypométabolisme du glucose au cerveau peut apparaître des décennies avant le diagnostic de maladie d’Alzheimer. Pourtant, le métabolisme des cétones, le carburant alternatif principal au glucose, n’est pas altéré, autant chez les personnes plus âgées que chez les personnes atteintes de la maladie d’Alzheimer. Les méthodes connues (diète cétogène, jeûne, huile de triglycérides de moyennes chaînes) pour augmenter la production de cétones comportent leurs inconvénients. L’objectif de ces projets était de vérifier l’efficacité de produits commerciaux vendus à cet effet et d’évaluer d’autres molécules qui pourraient être utilisées pour leur propriété cétogène. Ce sont des suppléments alimentaires pouvant servir de substrat pour la cétogenèse (butyrate, monoglycéride d’octanoate (O-MAG), leucine) ou de facilitateur du transport des acides gras (carnitine). Méthodes : Pour ce faire, les participants devaient se présenter au laboratoire pour plusieurs demi-journées d’étude d’une durée de 4 heures. Lors de ces journées, un des suppléments leur était servi avec un déjeuner et des prises de sang étaient effectuées toutes les 30 minutes. Résultats : Le produit commercial contenant des MCT, le butyrate, l’O-MAG et la leucine ont permis d’augmenter respectivement les concentrations maximales en cétones plasmatiques de 568, 226, 67 et 70 µmol/L (p≤0,05) par rapport au contrôle. De plus, la concentration plasmatique en octanoate était corrélée significativement avec la concentration sanguine d’acétoacétate (r=0,85 ; p <0,0001) et de β-hydroxybutyrate (r=0,58 ; p=0,01). L’aire sous la courbe par gramme de produit ingéré montre que le butyrate était le supplément cétogène le plus efficace et était plus cétogène que le produit commercial, l’O-MAG et la leucine (p=0,009). Discussion : Le butyrate était 3 fois plus cétogène que tous les autres suppléments testés. Par contre, son ingestion a causé quelques effets secondaires à certains participants. La leucine a été le seul supplément à ne créer aucun inconfort chez les participants. Il faudrait donc étudier la possibilité de combiner plusieurs molécules dans un supplément chimiquement pensé pour être le plus efficace possible et pour être intéressant lors d’une utilisation quotidienne.

Este trabalho tem como objetivo rever as relações existentes entre os valores obtidos dos ensaios mini-CBR e CBR, a fim de tornar possível a utilização dos resultados de ensaios de mini-CBR no dimensionamento de pavimentos flexíveis, uma vez que este ensaio é mais prático, exige menor quantidade de amostra, é mais rápido para ser executado e exige menor esforço físico na sua realização, sendo, portanto, menos dispendioso que o ensaio de CBR. No desenvolvimento dos ensaios, os resultados indicavam que essas relações não se mostravam adequadas para o universo em estudo, pois quando tentava-se relacionar, graficamente, os resultados dos ensaios tradicionais de CBR com os do mini-CBR, não se obtinham retas como era de se esperar e sim uma nuvem de pontos, indicando não haver correlação entre os dois índices. Desta forma, tentou-se desenvolver novas relações, nos moldes do que fora feito originalmente por Nogami (1972), e correlacionar novamente os valores de carga do ensaio de CBR, para as penetrações de 2,5 e 5,0 mm, com os valores de carga desenvolvidos nos ensaios padronizados de mini-CBR, para as penetrações de 2,0 e 2,5 mm, respectivamente, nas energias de compactação normal e intermediária. Nesta pesquisa são abordados os fundamentos, a descrição e algumas pesquisas realizadas com os ensaios de CBR e de mini-CBR. Foram utilizadas nesta pesquisa 62 amostras de solos do município de São Carlos - SP, as quais foram submetidas ao ensaio de CBR, nas energias de compactação normal e intermediária, e os resultados foram comparados com os dos ensaios de mini-CBR. As amostras foram escolhidas considerando-se a proporcionalidade entre as áreas de ocorrência das classes pedológicas no município de São Carlos. Por fim, apresentam-se as tentativas feitas para aproveitar ao máximo os resultados obtidos nos ensaios de CBR e de mini-CBR. / The objective of this work is to review the relation among the results of mini-CBR and CBR tests. This will make possible the use of mini-CBR tests results in flexible pavements design, once this test is more practical, it demands smaller amount of samples, it execution is faster and it demands less physical effort, being, therefore, less expensive than CBR tests. In the development this tests, the results indicated that those relations not shown appropriate for the universe in study, therefore when it tried to relation, graphically, the results of the traditional CBR test with the one of the mini-CBR, not obtained straight line as it was of waiting and yes a cloud of points, indicating not to be correlation among the two indexes. This form, tried to develop new relations, in the molds of what had been done originally by Nogami (1972), and to correlate the values of load CBR test, for the penetrations of 2,5 and 5,0 mm, with the load values developed in the standardized mini-CBR test, for the penetrations of 2,0 and 2,5 mm, respectively, in normal and intermediate compactation energies. In this tests are foundations, the description and some researches realized are approached with the CBR and mini-CBR tests. In this tests will used, 62 soils samples from São Carlos - SP, will be submitted to CBR test, in normal and intermediate compactation energies, and the results will be compared with those ones from mini-CBR test. The samples were chosen considering theproportionality among pedologic class occurrence areas in São Carlos. Finally, to show up the attempts done to utilize of to the maximum the results obtained in the CBR and mini-CBR tests.

Este trabalho tem como objetivo rever as relações existentes entre os valores obtidos dos ensaios mini-CBR e CBR, a fim de tornar possível a utilização dos resultados de ensaios de mini-CBR no dimensionamento de pavimentos flexíveis, uma vez que este ensaio é mais prático, exige menor quantidade de amostra, é mais rápido para ser executado e exige menor esforço físico na sua realização, sendo, portanto, menos dispendioso que o ensaio de CBR. No desenvolvimento dos ensaios, os resultados indicavam que essas relações não se mostravam adequadas para o universo em estudo, pois quando tentava-se relacionar, graficamente, os resultados dos ensaios tradicionais de CBR com os do mini-CBR, não se obtinham retas como era de se esperar e sim uma nuvem de pontos, indicando não haver correlação entre os dois índices. Desta forma, tentou-se desenvolver novas relações, nos moldes do que fora feito originalmente por Nogami (1972), e correlacionar novamente os valores de carga do ensaio de CBR, para as penetrações de 2,5 e 5,0 mm, com os valores de carga desenvolvidos nos ensaios padronizados de mini-CBR, para as penetrações de 2,0 e 2,5 mm, respectivamente, nas energias de compactação normal e intermediária. Nesta pesquisa são abordados os fundamentos, a descrição e algumas pesquisas realizadas com os ensaios de CBR e de mini-CBR. Foram utilizadas nesta pesquisa 62 amostras de solos do município de São Carlos - SP, as quais foram submetidas ao ensaio de CBR, nas energias de compactação normal e intermediária, e os resultados foram comparados com os dos ensaios de mini-CBR. As amostras foram escolhidas considerando-se a proporcionalidade entre as áreas de ocorrência das classes pedológicas no município de São Carlos. Por fim, apresentam-se as tentativas feitas para aproveitar ao máximo os resultados obtidos nos ensaios de CBR e de mini-CBR. / The objective of this work is to review the relation among the results of mini-CBR and CBR tests. This will make possible the use of mini-CBR tests results in flexible pavements design, once this test is more practical, it demands smaller amount of samples, it execution is faster and it demands less physical effort, being, therefore, less expensive than CBR tests. In the development this tests, the results indicated that those relations not shown appropriate for the universe in study, therefore when it tried to relation, graphically, the results of the traditional CBR test with the one of the mini-CBR, not obtained straight line as it was of waiting and yes a cloud of points, indicating not to be correlation among the two indexes. This form, tried to develop new relations, in the molds of what had been done originally by Nogami (1972), and to correlate the values of load CBR test, for the penetrations of 2,5 and 5,0 mm, with the load values developed in the standardized mini-CBR test, for the penetrations of 2,0 and 2,5 mm, respectively, in normal and intermediate compactation energies. In this tests are foundations, the description and some researches realized are approached with the CBR and mini-CBR tests. In this tests will used, 62 soils samples from São Carlos - SP, will be submitted to CBR test, in normal and intermediate compactation energies, and the results will be compared with those ones from mini-CBR test. The samples were chosen considering theproportionality among pedologic class occurrence areas in São Carlos. Finally, to show up the attempts done to utilize of to the maximum the results obtained in the CBR and mini-CBR tests.

<p>Selective therapeutic targeting of tumors requires identification of differences between the homeostatic requirements of cancer and host cells. One such difference is the manner in which cancer cells acquire energy. Cancer cells often grow in an environment of local hypoxia; under these conditions tumor cells depend on glycolysis for energy, but are unable to perform oxidative phosphorylation. Many tumor cells, despite normoxic conditions, continue to perform glycolysis without oxidative phosphorylation. The net result of glycolysis without oxidative phosphorylation is twofold: the need to consume a greater amount of glucose than a non-cancerous host cell, and the burden of increased intracellular lactic acid. The proteins responsible for the transport of lactic acid in and out of cells are known as the monocarboxylate transporters (MCTs). Monocarboxylate Transporter 1 (MCT1) and Monocarboxylate Transporter 4 (MCT4) are the MCTs that play a major role in the transport of lactic acid. Tumor cells depend on MCT1 and MCT4 activity to excrete excess intracellular lactic acid to maintain neutral intracellular pH and homeostasis. Using human neuroblastoma and prostate cancer cell lines this work demonstrates that tumor cells can be selectively targeted tumor under conditions of hypoxia or acidosis in vitro with the drug lonidamine, with a small molecule inhibitor selective for MCT1, or with RNA interference of MCT1. Inhibition of MCT1 activity in neuroblastoma cells under acidic extracellular conditions results in intracellular acidification and cell death. MCT1 mRNA is expressed in human neuroblastoma and positively correlated with clinical risk profile. Inhibition of MCT1 activity in hypoxic prostate cancer cells results in a reduction of lactate excretion, decreased intracellular pH, inhibition of ATP production, and subsequent cell death. MCT1 expression in sections of human prostate tumors has been demonstrated to validate MCT1 as a target in prostate cancer.</p> <p>Through the Pasteur and Warburg effects, tumors have an increased demand for glucose. Some cancers store glycogen, but the reasons for this are largely unknown. It is hypothesized that tumor glycogen is used to promote tumor survival during transient hypoxia or low glucose, and that the mechanisms by which glycogen is stored is a potential therapeutic target in cancer. Tumors from human cell lines (WiDr, PC3, FaDu) have been grown in nude mice, sectioned and stained to measure glycogen storage. Using consecutive frozen sections, levels of hypoxia, glucose, lactate, ATP, and CD31, an endothelial cell marker, have been determined. These sections have been employed to elucidate the "architecture" of tumor metabolism in terms of vessel distance. Additionally, PAS-stained EF5 labeled human tumor samples were used to obtain calibrated hypoxia measurements to correlate with PAS. These studies demonstrate a correlation between hypoxia and the formation of glycogen deposits in human tumors and nude mouse xenografts. In cell culture, formation of glycogen deposits after exposure to hypoxia has been demonstrated, in addition to expression of glycogen synthase in human cancer cell lines.</p> <p>The development of novel selective cancer chemotherapeutics will require the identification of differences between cancerous cells and normal host cells to exploit as targets. Several differences in metabolism, including the need to excrete excess lactic acid and store glycogen under hypoxic conditions, are such targets. Novel therapeutics exploiting these targets should be effective against cancer cells and minimally toxic to host cells.</p> / Dissertation