Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed with DCs with the aim of measuring the release and gene expression of inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1, Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation. Addition of NO before LPS-induced maturation strongly inhibited the release of IL-12, while increasing the expression and release of IL-23, IL-1β and IL-6, which are all involved in Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β. Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

Impact of T cell receptor affinity on the molecular mechanisms modulating CD8 T cell signalling and function against NY-ESO-1 tumour antigen

It is well established that cytotoxic T lymphocytes play a pivotal role in the protection against intracellular pathogens and tumour cells. Such protective immune responses rely on the specific T cell receptor (TCR)-mediated recognition by CD8 T cells of small antigenic peptides presented in the context of class-I Major Histocompatibility Complex molecules (pMHCs) on the surface of infected or malignant cells. The strength (affinity/avidity) of this interaction is a major correlate of protection. Although tumour-reactive CD8 T cells can be observed in cancer patients, anti-tumour immune responses are often ineffective in controlling or eradicating the disease due to the relative low TCR affinity of these cells. To overcome this limitation, tumour-specific CD8 T cells can be genetically modified to express TCRs of improved binding strength against a defined tumour antigen before adoptive cell transfer into cancer patients. We previously generated a panel of TCRs specific for the cancer-testis antigen NY-ESO-l,57.165 with progressively increased affinities for the pMHC complex, thus providing us with a unique tool to investigate the causal link between the surface expression of such TCRs and T cell activation and function. We recently demonstrated that anti-tumour CD8 T cell reactivity could only be improved within physiological affinity limits, beyond which drastic functional declines were observed, suggesting the presence of multiple regulatory mechanisms limiting T cell activation and function in a TCR affinity-dependent manner. The overarching goal of this thesis was (i) to assess the precise impact of TCR affinity on T cell activation and signalling at the molecular level and (ii) to gain further insights on the mechanisms that regulate and delimitate maximal/optimized CD8 T cell activation and signalling. Specifically, by combining several technical approaches we characterized the activation status of proximal (i.e. CD3Ç, Lek, and ZAP-70) and distal (i.e. ERK1/2) signalling molecules along the TCR affinity gradient. Moreover, we assessed the extent of TCR downmodulation, a critical step for initial T cell activation. CD8 T cells engineered with the optimal TCR affinity variants showed increased activation levels of both proximal and distal signalling molecules when compared to the wild-type T cells. Our analyses also highlighted the "paradoxical" status of tumour-reactive CD8 T cells bearing very high TCR affinities, which retained strong proximal signalling capacity and TCR downmodulation, but were unable to propagate signalling distally (i.e. pERKl/2), resulting in impaired cell-mediated functions. Importantly, these very high affinity T cells displayed maximal levels of SHP-1 and SHP-2 phosphatases, two negative regulatory molecules, and this correlated with a partial pERKl/2 signalling recovery upon pharmacological SHP-l/SHP-2 inhibition. These findings revealed the putative presence of inhibitory regulators of the TCR signalling cascade acting very rapidly following tumour-specific stimulation. Moreover, the very high affinity T cells were only able to transiently express enhanced proximal signalling molecules, suggesting the presence of an additional level of regulation that operates through the activation of negative feedback loops over time, limiting the duration of the TCR-mediated signalling. Overall, the determination of TCR-pMHC binding parameters eliciting optimal CD8 T cell activation, signalling, and effector function while guaranteeing high antigen specificity, together with the identification of critical regulatory mechanisms acting proximally in the TCR signalling cascade, will directly contribute to optimize and support the development of future TCR-based adoptive T cell strategies for the treatment of malignant diseases. -- Les lymphocytes T CD8 cytotoxiques jouent un rôle prédominant dans la protection contre les pathogènes intracellulaires et les cellules tumorales. Ces réponses immunitaires dépendent de la spécificité avec laquelle les récepteurs T (TCR) des lymphocytes CD8 reconnaissent les peptides antigéniques présentés par les molécules du complexe Majeur de Histocompatibilité de classe I (pCMH) à la surface des cellules infectées ou malignes. La force (ou affinité/avidité) de l'interaction du TCR-pCMH est un corrélat majeur de protection. Les réponses immunitaires sont cependant souvent inefficaces et ne permettent pas de contrôler ou d'éliminer les cellules tumorales chez les patients atteint du cancer, et ce à cause de la relative faible reconnaissance des TCRs exprimés par les lymphocytes T CD8 envers les antigènes tumoraux. Afin de surmonter cette limitation, les cellules T anti-tumorales peuvent être génétiquement modifiées en les dotant de TCRs préalablement optimisés afin d'augmenter leur reconnaissance ou affinité contre les antigènes tumoraux, avant leur ré¬infusion dans le patient. Nous avons récemment généré des cellules T CD8 exprimant un panel de TCRs spécifiques pour l'antigène tumoral NY-ESO-l157.16J avec des affinités croissantes, permettant ainsi d'investiguer la causalité directe entre l'affinité du TCR-pCMH et la fonction des cellules T CD8. Nous avons démontré que la réactivité anti-tumorale pouvait être améliorée en augmentant l'affinité du TCR dans une intervalle physiologique, mais au delà duquel nous observons un important déclin fonctionnel. Ces résultats suggèrent la présence de mécanismes de régulation limitant l'activation des cellules T de manière dépendante de l'affinité du TCR. Le but de cette thèse a été (i) de définir l'impact précis de l'affinité du TCR sur l'activation et la signalisation des cellules T CD8 au niveau moléculaire et (ii) d'acquérir de nouvelles connaissances sur les mécanismes qui régulent et délimitent l'activation et la signalisation maximale des cellules T CD8 optimisées. Spécifiquement, en combinant plusieurs approches technologiques, nous avons caractérisé l'état d'activation de différentes protéines de la voie de signalisation proximale (CD3Ç, Lek et ZAP-70) et distale (ERK1/2) le long du gradient d'affinité du TCR, ainsi que l'internalisation du TCR, une étape clef dans l'activation initiale des cellules T. Les lymphocytes T CD8 exprimant des TCRs d'affinité optimale ont montré des niveaux d'activation augmentés des molécules proximales et distales par rapport aux cellules de type sauvage (wild-type). Nos analyses ont également mis en évidence un paradoxe chez les cellules T CD8 équipées avec des TCRs de très haute affinité. En effet, ces cellules anti-tumorales sont capables d'activer leurs circuits biochimiques au niveau proximal et d'internaliser efficacement leur TCR, mais ne parviennent pas à propager les signaux biochimiques dépendants du TCR jusqu'au niveau distal (via phospho-ERKl/2), avec pour conséquence une limitation de leur capacité fonctionnelle. Finalement, nous avons démontré que SHP-1 et SHP-2, deux phosphatases avec des propriétés régulatrices négatives, étaient majoritairement exprimées dans les cellules T CD8 de très hautes affinités. Une récupération partielle des niveaux d'activation de ERK1/2 a pu être observée après l'inhibition pharmacologique de ces phosphatases. Ces découvertes révèlent la présence de régulateurs moléculaires qui inhibent le complexe de signalisation du TCR très rapidement après la stimulation anti-tumorale. De plus, les cellules T de très hautes affinités ne sont capables d'activer les molécules de la cascade de signalisation proximale que de manière transitoire, suggérant ainsi un second niveau de régulation via l'activation de mécanismes de rétroaction prenant place progressivement au cours du temps et limitant la durée de la signalisation dépendante du TCR. En résumé, la détermination des paramètres impliqués dans l'interaction du TCR-pCMH permettant l'activation de voies de signalisation et des fonctions effectrices optimales ainsi que l'identification des mécanismes de régulation au niveau proximal de la cascade de signalisation du TCR contribuent directement à l'optimisation et au développement de stratégies anti-tumorales basées sur l'ingénierie des TCRs pour le traitement des maladies malignes.

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Triggering the generation of an iron(IV)-oxo compound and its reactivity toward sulfides by RuII photocatalysis

The preparation of [FeIV(O)(MePy2tacn)]2+ (2, MePy2tacn = N-methyl-N,N-bis(2-picolyl)-1,4,7-triazacyclononane) by reaction of [FeII(MePy2tacn)(solvent)]2+ (1) and PhIO in CH3CN and its full characterization are described. This compound can also be prepared photochemically from its iron(II) precursor by irradiation at 447 nm in the presence of catalytic amounts of [Ru II(bpy)3]2+ as photosensitizer and a sacrificial electron acceptor (Na2S2O8). Remarkably, the rate of the reaction of the photochemically prepared compound 2 toward sulfides increases 150-fold under irradiation, and 2 is partially regenerated after the sulfide has been consumed; hence, the process can be repeated several times. The origin of this rate enhancement has been established by studying the reaction of chemically generated compound 2 with sulfides under different conditions, which demonstrated that both light and [Ru II(bpy)3]2+ are necessary for the observed increase in the reaction rate. A combination of nanosecond time-resolved absorption spectroscopy with laser pulse excitation and other mechanistic studies has led to the conclusion that an electron transfer mechanism is the most plausible explanation for the observed rate enhancement. According to this mechanism, the in-situ-generated [RuIII(bpy)3] 3+ oxidizes the sulfide to form the corresponding radical cation, which is eventually oxidized by 2 to the corresponding sulfoxide

A Novel Missense Mutation, I890T, in the Pore Region of Cardiac Sodium Channel Causes Brugada Syndrome

Brugada syndrome (BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na₊ channel alpha subunit (Naᵥ1.5). The aim of this work was to characterize the functional alterations caused by a novel SCN5A mutation, I890T, and thus establish whether this mutation is associated with BrS. The mutation was identified by direct sequencing of SCN5A from the proband’s DNA. Wild-type (WT) or I890T Naᵥ1.5 channels were heterologously expressed in human embryonic kidney cells. Sodium currents were studied using standard whole cell patch-clamp protocols and immunodetection experiments were performed using an antibody against human Naᵥ1.5 channel. A marked decrease in current density was observed in cells expressing the I890T channel (from -52.0 ± 6.5 pA/pF, n=15 to 35.9 ± 3.4 pA/pF, n = 22, at -20 mV, WT and I890T, respectively). Moreover, a positive shift of the activation curve was identified (V½ =-32.0 ± 0.3 mV, n = 18, and -27.3 ± 0.3 mV, n = 22, WT and I890T, respectively). No changes between WT and I890T currents were observed in steady-state inactivation, time course of inactivation, slow inactivation or recovery from inactivation parameters. Cell surface protein biotinylation analyses confirmed that Nav1.5 channel membrane expression levels were similar in WT and I890T cells. In summary, our data reveal that the I890T mutation, located within the pore of Nav1.5, causes an evident loss-of-function of the channel. Thus, the BrS phenotype observed in the proband is most likely due to this mutation

Características de la conducta de fumar en función de la fase de abandono en una muestra de personal de la Universidad de Girona

Objetivos: Determinar la prevalencia y las características de la conductade fumar y la distribución por estadios de abandono del tabaquismoentre el personal de la Universidad de Girona.Pacientes y método: Se diseñó un estudio descriptivo transversal.Para ello se realizó una entrevista sobre la conducta de fumar a una muestrarepresentativa de los 941 miembros del personal de la Universidadde Girona en el segundo semestre de 1999.Resultados: De los 281 participantes en el estudio, 77 (27,4%) eranfumadores, 67 (23,9%) exfumadores y 137 (48,7%) no fumadores. PorFacultades, la mayor prevalencia de fumadores se encontró en: Letras:38,9%; Ciencias de la Educación: 31% y Enfermería: 28,3%. La distribuciónde los sujetos por etapas de abandono fue la siguiente: precontemplación:36,8%; contemplación: 13,2%; preparación: 3,5%; acción:3,5% y mantenimiento: 43%. El consumo de tabaco light fue del49,1% en precontemplación, 47,1% en contemplación y 33,3% en preparación.Respondieron haber recibido consejo médico para dejar de fumar:precontemplación: 35,8%; contemplación: 52,6%, preparación:60%, acción: 20% y mantenimiento: 24,2%.Conclusiones: 1. Las Facultades relacionadas con el ámbito de lasalud, Ciencias de la Educación y Enfermería son, junto con las de Letraslas que presentan mayor consumo de tabaco. 2. Los fumadores en precontemplación,en comparación con los sujetos en contemplación y preparación,informan con mayor frecuencia de consumir tabaco bajo ennicotina y de no haber recibido consejo médico

Antioxidant capacity of eugenol derivatives

Toxicity and antioxidant capacity of eugenol derivatives (E2 = 2-Methoxy-4-[1-propenylphenyl]acetate, E3 = 4-Allyl-2-methoxyphenylacetate, E4 = 4-Allyl-2-methoxy-4-nitrophenol, E5 = 5-Allyl-3-nitrobenzene-1,2-diol, E6 = 4-Allyl-2-methoxy-5-nitrophenyl acetate) were evaluated in order to determine the influence of the sustituents. E2-E6 were synthesized from eugenol (E1). E1 was extracted from cloves oil, and E2-E6 were obtained through acetylation and nitration reactions. Antioxidant capacity evaluated by DPPH (1, 1-Diphenyl-2-picrylhydrazil) and ORAC fluorescein demonstrated that E1 and E5 have a higher capacity and the minor toxicity evaluated by red blood cells haemolysis and the Artemia saline test. In accordance with our results, the compound's (E1-E5) use in the pharmaceutical, cosmetic and or food industries could be suggested.

Anchor or Accelerate – A Study on Cancer Cell Adhesion and Motility

Cell migration and adhesion to the extracellular matrix (ECM) are crucial in many biological and pathological processes such as morphogenesis, tissue repair, inflammatory responses, survival, and cancer. Cell-matrix adhesion is mediated by the integrin family of transmembrane receptors, which not only anchor cells to their surroundings, but also transmit bidirectional signalling at the cell surface and couple the ECM to the cytoskeleton. Another group of adhesion receptors are the syndecan proteoglycans, which engage the ECM and possess signalling activity in response to a variety of ligands. Cell migration is a complex process that requires spatial and temporal coordination of adhesion, cell contractility, intracellular traffic of integrins, and matrix turnover by matrix metalloproteinases (MMPs). Thus, integrins and syndecans, as well as MMPs, play essential roles in cancer cell migration and invasion. The understanding of the cooperation of syndecans and integrins was broadened in this thesis study. The results reveal that syndecan-1 functions in concert with 21 integrin in cell adhesion to collagen, whereas syndecan-4 is essential in 21 integrin-mediated matrix contraction. Finally, oncogenic K-Ras was shown to regulate 21 integrin, membrane-type 1 MMP, and syndecan-1 and -4 expression and their cooperation in cell invasion. Epithelial-mesenchymal transition (EMT) is fundamental during embryogenesis and organ development. Activation of EMT processes, including the upregulation of mesenchymal intermediate filament protein vimentin, has also been implicated in the acquisition of a malignant phenotype by epithelial cancer cells. Members of the protein kinase C (PKC) superfamily are involved in cell migration and various integrindependent cellular functions. One aim of this work was to shed light on the role of vimentin in the regulation of integrin traffic and cell motility. In addition, the mechanism by which vimentin participates in EMT was investigated. The results show that integrin recycling and motility are dependent on the PKC–mediated phosphorylation of vimentin. In addition, vimentin was found to be a positive regulator of EMT and regulate the expression of several migratory genes. Specifically, vimentin governs the expression of receptor tyrosine kinase Axl, which is implicated in tumour growth and metastasis. Taken together, the findings described in this thesis reveal novel aspects of the complex interplay between distinct cellular components: integrins, syndecans, and the vimentin cytoskeleton, which all contribute to the regulation of human cancer cell adhesion, migration, and invasion.

Hydrocortisone decreases apoptosis in jejunum of horses subjected to experimental ischemia and reperfusion

In order to evaluate the effect of hydrocortisone on apoptosis in the jejunum of horses subjected to ischemia and reperfusion, ten horses were paired and grouped into two groups - treated (n=5) and non treated (n=5). Segments of the jejunum were used as controls (C), or as venous ischemia (VIsc), which were subjected to 2h of ischemia followed by 2 or 12h of reperfusion. C samples were collected at time zero (prior to ischemia) and VIsc samples were collected at 2h of ischemia and at 2 and 12h of reperfusion. TUNEL positive apoptotic cells were counted in 10 microscopical fields in deep mucosa from each horse throughout the time course. After 12h of reperfusion, the number of apoptotic cells in treated group were significantly lower than in untreated animals, indicating that hydrocortisone inhibits apoptosis. These results indicate that hydrocortisone has a beneficial effects favoring the maintenance of jejunal integrity in horses with ischemia and reperfusion injuries by preventing apoptotic cell death.

Occurrence and molecular characterization of cryptococcosis in dogs and cats in Mato Grosso, Brazil

Cryptococcosis is an infection that affects humans and animals, the etiology is attributed to Cryptococcus neoformans variety neoformans, C. neoformans var. grubii and Cryptococcus gattii. The infection is common in dogs and cats, causing respiratory, neurological, cutaneous and ocular infections. Aiming to better understand the epidemiology of cryptococcosis in animals in the region, this paper describe the occurrence and characterization of the Cryptococcus species involved in this illness in pet animals at Mato Grosso State, Brazil. Clinical samples of four cases, two in cats and two dogs, were submitted for pathological, microbiological and molecular analysis. Microscopically, in three cases, tissue sections stained with hematoxylin and eosin had absence to severe granulomatous reaction composed by histiocytes, multinucleated cells and lymphocytes infiltration. In one case, citological imprint analysis showed similar inflammatory mainly mononuclear and lymphocyte cells infiltration. All cases had variable amounts of intracellular and extracellular fungal structures compatible with Cryptococcus sp. on Periodic Acid-Schiff (PAS) stain. All clinical samples were positive for culture on Sabouraud Dextrose Agar (SDA) and morphologically classified as Cryptococcus sp. The isolates were PCR positive for C. gatti, being confirmed by sequencing technique. The findings characterize the molecular species involved in animal infections in the region, and may contribute to future studies of the epidemiology of C. gattii.

Vegetative organ anatomy of Ianthopappus corymbosus Roque & Hind (Asteraceae-Mutisieae)

A study on the vegetative organ anatomy of Ianthopappus corymbosus was conducted in order to provide a basis for comparison with the genus Richterago, since this species had been previously included in that genus. The anatomical characters of I. corymbosus that support its exclusion from the genus Richteragon are: epithelial cell organization of adventitious root secretory canals, non-glandular trichomes, and presence of cortical vascular bundles in the stem. In Ianthopappus corymbosus, the underground system consists of rhizophore from which adventitious roots branch off. The subapical meristem of the adventitious root revealed that the ground meristem forms the inner layer which in a meristematic phase, forms 2/3 of the cortex. This layer will differentiate in the endodermis, with Casparian strips, and is referred to as meristematic endodermis. Endodermic secretory canals, limited by four epithelial cells, appear in the region adjacent to the primary phloem.

Rotavirus and reovirus interaction with mouse peritoneal resident phagocytic cells

Rotaviruses and reoviruses are involved in human and animal diseases. It is known that both viruses penetrate the gastrointestinal tract but their interaction with phagocytic cells is unknown. To study this interaction, peritoneal resident phagocytic cells were used and rotavirus and reovirus replication in peritoneal phagocytic cells was observed. However, rotavirus replication in these cells led to the production of defective particles since MA-104 cells inoculated with rotavirus phagocytic cell lysate did not show any evidence of virus replication. On the basis of these results, we suggest that, although reovirus dissemination may be helped by these phagocytic cells, these cells may control rotavirus infection and probably contribute to the prevention of its dissemination.

Cytokine profiles during experimental Chagas' disease

People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-g in both mouse strains. However, the amount of IFN-g in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

Autoradiography reveals regional metabolic differences in the endometrium of pregnant and nonpregnant mice

The rodent endometrium undergoes remarkable modifications during pregnancy, resulting from a redifferentiation of its fibroblasts. During this modification (decidualization), the fibroblasts transform into large, polyhedral cells that establish intercellular junctions. Decidualization proceeds from the subepithelial stroma towards the deep stroma situated next to the myometrium and creates regions composed of cells in different stages of differentiation. We studied by autoradiography whether cells of these different regions have different levels of macromolecular synthesis. Radioactive amino acids or radioactive sulfate were administered to mice during estrus or on different days of pregnancy. The animals were killed 30 min after injection of the precursors and the uteri were processed for light microscope autoradiography. Silver grains were counted over cells of different regions of the endometrium and are reported as the number of silver grains per area. Higher levels of incorporation of amino acids were found in pregnant animals as compared to animals in estrus. In pregnant animals, the region of decidual cells or the region of fibroblasts transforming into decidual cells showed the highest levels of synthesis. Radioactive sulfate incorporation, on the other hand, was generally higher in nonpregnant animals. Animals without decidual cell transformation (nonpregnant and 4th day of pregnancy) showed a differential incorporation by subepithelial and deep stroma fibroblasts. This study shows that regional differences in synthetic activity exist in cells that are in different stages of transformation into decidual cells as well as in different regions of the endometrium of nonpregnant mice

Effect of Walker 256 tumor growth on intestinal absorption of leucine, methionine and glucose in newly weaned and mature rats

In tumor-bearing rats, most of the serum amino acids are used for synthesis and oxidation processes by the neoplastic tissue. In the present study, the effect of Walker 256 carcinoma growth on the intestinal absorption of leucine, methionine and glucose was investigated in newly weaned and mature rats. Food intake and carcass weight were decreased in newly weaned (NT) and mature (MT) rats bearing Walker 256 tumor in comparison with control animals (NC and MC). The tumor/carcass weight ratio was higher in NT than in MT rats, whereas nitrogen balance was significantly decreased in both as compared to control animals. Glucose absorption was significantly reduced in MT rats (MT = 47.3 ± 4.9 vs MC = 99.8 ± 5.3 nmol min-1 cm-1, Kruskal-Wallis test, P<0.05) but this fact did not hamper the evolution of cancer. There was a significant increase in methionine absorption in both groups (NT = 4.2 ± 0.3 and MT = 2.0 ± 0.1 vs NC = 3.7 ± 0.1 and MC = 1.2 ± 0.2 nmol min-1 cm-1, Kruskal-Wallis test, P<0.05), whereas leucine absorption was increased only in young tumor-bearing rats (NT = 8.6 ± 0.2 vs NC = 7.7 ± 0.4 nmol min-1 cm-1, Kruskal-Wallis test, P<0.05), suggesting that these metabolites are being used for synthesis and oxidation processes by the neoplastic cells, which might ensure their rapid proliferation especially in NT rats.