The host Rab9a/Rab32 axis is actively recruited to the Trypanosoma cruzi parasitophorous vacuole and benefits the infection cycle.

Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoan parasite that infects phagocytic and non-phagocytic mammalian cells. At early stages of infection, trypomastigotes, the infective forms of this parasite, localize in a vesicular compartment called the T. cruzi parasitophorous vacuole until the exit of parasites to the host cell cytoplasm where continue their infective cycle. Rab proteins participate in the membrane traffic's molecular machinery, functioning as central regulators of vesicle recognition and transport. In previous work, we demonstrated that endocytic Rabs are key factors of the T. cruzi infection process in non-phagocytic cells, regulating the formation and the maturation of the vacuole. In this work, we identified and characterized other molecular components of the vesicular transport pathways and their participation in the T. cruzi infection. We found that Rab9a and Rab32, two regulators of the endocytic and autophagic pathways, were actively recruited to the T. cruzi vacuoles and favored the late stages of the infective process. The recruitment was specific and dependent on T. cruzi protein synthesis. Interestingly, Rab32 association depends on the presence of Rab9a in the vacuolar membrane, while the inhibition of the cysteine-protease cruzipain, a T. cruzi virulence factor, significantly decreases both Rab9a and Rab32 association with the vacuole. In summary, this work showed for the first time that specific molecules produced and secreted by the parasite can subvert intracellular components of host cells to benefit the infection. These new data shed light on the complex map of interactions between T. cruzi and the host cell and introduce concepts that can be useful in finding new forms of intervention against this parasite in the future.

Repurposing Carvedilol as a Novel Inhibitor of the Trypanosoma cruzi Autophagy Flux That Affects Parasite Replication and Survival.

T. cruzi, the causal agent of Chagas disease, is a parasite able to infect different types of host cells and to persist chronically in the tissues of human and animal hosts. These qualities and the lack of an effective treatment for the chronic stage of the disease have contributed to the durability and the spread of the disease around the world. There is an urgent necessity to find new therapies for Chagas disease. Drug repurposing is a promising and cost-saving strategy for finding new drugs for different illnesses. In this work we describe the effect of carvedilol on T. cruzi. This compound, selected by virtual screening, increased the accumulation of immature autophagosomes characterized by lower acidity and hydrolytic properties. As a consequence of this action, the survival of trypomastigotes and the replication of epimastigotes and amastigotes were impaired, resulting in a significant reduction of infection and parasite load. Furthermore, carvedilol reduced the whole-body parasite burden peak in infected mice. In summary, in this work we present a repurposed drug with a significant in vitro and in vivo activity against T. cruzi. These data in addition to other pharmacological properties make carvedilol an attractive lead for Chagas disease treatment.

Endocytic Rabs Are Recruited to the Trypanosoma cruzi Parasitophorous Vacuole and Contribute to the Process of Infection in Non-professional Phagocytic Cells.

Trypanosoma cruzi is the parasite causative of Chagas disease, a highly disseminated illness endemic in Latin-American countries. T. cruzi has a complex life cycle that involves mammalian hosts and insect vectors both of which exhibits different parasitic forms. Trypomastigotes are the infective forms capable to invade several types of host cells from mammals. T. cruzi infection process comprises two sequential steps, the formation and the maturation of the Trypanosoma cruzi parasitophorous vacuole. Host Rab GTPases are proteins that control the intracellular vesicular traffic by regulating budding, transport, docking, and tethering of vesicles. From over 70 Rab GTPases identified in mammalian cells only two, Rab5 and Rab7 have been found in the T. cruzi vacuole to date. In this work, we have characterized the role of the endocytic, recycling, and secretory routes in the T. cruzi infection process in CHO cells, by studying the most representative Rabs of these pathways. We found that endocytic Rabs are selectively recruited to the vacuole of T. cruzi, among them Rab22a, Rab5, and Rab21 right away after the infection followed by Rab7 and Rab39a at later times. However, neither recycling nor secretory Rabs were present in the vacuole membrane at the times studied. Interestingly loss of function of endocytic Rabs by the use of their dominant-negative mutant forms significantly decreases T. cruzi infection. These data highlight the contribution of these proteins and the endosomal route in the process of T. cruzi infection.

Working together for the family: determination of HER oncogene co-amplifications in breast cancer.

HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r 2 = 0,91, p < 0,0001), CISH (Adjusted r 2 = 0,938, p < 0,0001) and IHC (Adjusted r 2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.

[Living in the midst of miasmas: The social issue of Chile between 1880 and 1920]. / Viviendo entre miasmas: en torno a la cuestión social, Chile de 1880 a 1920.

INTRODUCTION: The social issue in Chile stems from an accumulation of social problems resulting from the migratory movements of the countryside-city and mining areas. The cities did not have the hygienic conditions necessary to receive migrants, which caused housing and health problems within the population. OBJECTIVE: To analyze the problems of housing, hygiene, and health in Chile between 1880-1920. METHOD: We conduct a qualitative, analytical, and interpretive study using primary sources for the categories of analysis around housing, hygiene, and health of the following cities in Chile: Santiago, Valparaíso, Concepción and Chillán. RESULTS: The economic modernization led to the development of public works in the main cities of Chile, which also experienced a demographic phenomenon known as field-city migration, with urban growth never before seen. In the cities, there were problems of housing, hygiene, and health for the popular urban sectors. CONCLUSION: The State passed laws to regulate the conditions of the conventillos and public spaces to mitigate diseases and vices of the population.

INTRODUCCIÓN: La cuestión social tiene su origen en la acumulación de problemas sociales, producto de los movimientos migratorios del campo-ciudad y zonas mineras. Las ciudades no contaban con las condiciones higiénicas necesarias para recibir a los migrantes, lo cual provocó problemas de vivienda y salubridad entre la población. OBJETIVO: Analizar los problemas de vivienda, higiene y salubridad en Chile entre los años 1880 y 1920. MÉTODO: Es un estudio cualitativo, analítico e interpretativo, se utilizaron fuentes primarias para las categorías de análisis en torno a la vivienda, higiene y salubridad de las siguientes ciudades de Chile: Santiago, Valparaíso, Concepción y Chillán. RESULTADOS: La modernización económica permitió el desarrollo de obras públicas en las principales ciudades de Chile, pero también experimentaron un fenómeno demográfico conocido como migración campo - ciudad, con un crecimiento urbano nunca visto. CONCLUSIÓN: En las ciudades se presentaron problemas de vivienda, higiene y salubridad para los sectores populares urbanos. El Estado, a través de leyes, reguló las condiciones de los conventillos y espacios públicos con el propósito de mitigar enfermedades y vicios de la población.

Viviendo entre miasmas: en torno a la cuestión social, Chile de 1880 a 1920 / Living in the midst of miasmas: the social issue of Chile between 1880 and 1920

INTRODUCCIÓN: La cuestión social tiene su origen en la acumulación de problemas sociales, producto de los movimientos migratorios del campo-ciudad y zonas mineras. Las ciudades no contaban con las condiciones higiénicas necesarias para recibir a los migrantes, lo cual provocó problemas de vivienda y salubridad entre la población. OBJETIVO: Analizar los problemas de vivienda, higiene y salubridad en Chile entre los años 1880 y 1920. MÉTODO: Es un estudio cualitativo, analítico e interpretativo, se utilizaron fuentes primarias para las categorías de análisis en torno a la vivienda, higiene y salubridad de las siguientes ciudades de Chile: Santiago, Valparaíso, Concepción y Chillán. Resultados: La modernización económica permitió el desarrollo de obras públicas en las principales ciudades de Chile, pero también experimentaron un fenómeno demográfico conocido como migración campo - ciudad, con un crecimiento urbano nunca visto. CONCLUSIÓN: En las ciudades se presentaron problemas de vivienda, higiene y salubridad para los sectores populares urbanos. El Estado, a través de leyes, reguló las condiciones de los conventillos y espacios públicos con el propósito de mitigar enfermedades y vicios de la población.

INTRODUCTION: The social issue in Chile stems from an accumulation of social problems resulting from the migratory movements of the countryside-city and mining areas. The cities did not have the hygienic conditions necessary to receive migrants, which caused housing and health problems within the population. OBJECTIVE: To analyze the problems of housing, hygiene, and health in Chile between 1880-1920. METHOD: We conduct a qualitative, analytical, and interpretive study using primary sources for the categories of analysis around housing, hygiene, and health of the following cities in Chile: Santiago, Valparaíso, Concepción and Chillán. Results: The economic modernization led to the development of public works in the main cities of Chile, which also experienced a demographic phenomenon known as field-city migration, with urban growth never before seen. In the cities, there were problems of housing, hygiene, and health for the popular urban sectors. CONCLUSION: The State passed laws to regulate the conditions of the conventillos and public spaces to mitigate diseases and vices of the population.

The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis.

Autophagy is a cellular process required for the removal of aged organelles and cytosolic components through lysosomal degradation. All types of eukaryotic cells from yeasts to mammalian cells have the machinery to activate autophagy as a result of many physiological and pathological situations. The most frequent stimulus of autophagy is starvation and the result, in this case, is the fast generation of utilizable food (e.g. amino acids and basic nutrients) to maintain the vital biological processes. In some organisms, starvation also triggers other associated processes such as differentiation. The protozoan parasite Trypanosoma cruzi undergoes a series of differentiation processes throughout its complex life cycle. Although not all autophagic genes have been identified in the T. cruzi genome, previous works have demonstrated the presence of essential autophagic-related proteins. Under starvation conditions, TcAtg8, which is the parasite homolog of Atg8/LC3 in other organisms, is located in autophagosome-like vesicles. In this work, we have characterized the autophagic pathway during T. cruzi differentiation from the epimastigote to metacyclic trypomastigote form, a process called metacyclogenesis. We demonstrated that autophagy is stimulated during metacyclogenesis and that the induction of autophagy promotes this process. Moreover, with exception of bafilomycin, other classical autophagy modulators have similar effects on T. cruzi autophagy. We also showed that spermidine and related polyamines can positively regulate parasite autophagy and differentiation. We concluded that both polyamine metabolism and autophagy are key processes during T. cruzi metacyclogenesis that could be exploited as drug targets to avoid the parasite cycle progression.

Identification and characteristics of extracellular vesicles from bovine blastocysts produced in vitro.

Extracellular vesicles (EVs) have been identified within different body fluids and cell culture media. However, there is very little information on the secretion of these vesicles during early embryonic development. The aims of this work were first to demonstrate the secretion of extracellular vesicles by pre-implantation bovine embryos and second to identify and characterize the population of EVs secreted by bovine blastocysts during the period from day seven to nine of embryo culture and its correlation with further embryo development up to day 11. Bovine embryos were produced by in vitro fertilization (IVF) or parthenogenetic activation (PA) and cultured until blastocyst stage. Blastocyst selection was performed at day 7 post IVF/PA considering two variables: stage of development and quality of embryos. Selected blastocysts were cultured in vitro for 48 hours in groups (exp. 1) or individually (exp. 2) in SOF media depleted of exosomes. At day 9 post IVF/PA the media was collected and EVs isolated by ultracentrifugation. Transmission electron microscopy revealed the presence of heterogeneous vesicles of different sizes and population: microvesicles (MVs) and exosomes (EXs) of rounded shape, enclosed by a lipid bi-layer and ranging from 30 to 385 nm of diameter. Flow cytometry analysis allowed identifying CD63 and CD9 proteins as exosome markers. Nanoparticle tracking analysis generated a large number of variables, which required the use of multivariate statistics. The results indicated that the concentration of vesicles is higher in those blastocysts with arrested development from day 9 up to day 11 of in vitro development (6.7 x 108 particles/ml) derived from IVF (p <0.05), compared to PA blastocysts (4.7 x 108 particles/ml). Likewise, the profile (concentration and diameter) of particles secreted by embryos derived from IVF were different from those secreted by PA embryos. In conclusion, we demonstrated that bovine blastocysts secrete MVs/EXs to the culture media. Data suggest that characteristics of the population of EVs vary depending on embryo competence.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors required during Trypanosoma cruzi parasitophorous vacuole development.

Trypanosoma cruzi, the etiologic agent of Chagas disease, is an obligate intracellular parasite that exploits different host vesicular pathways to invade the target cells. Vesicular and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are key proteins of the intracellular membrane fusion machinery. During the early times of T. cruzi infection, several vesicles are attracted to the parasite contact sites in the plasma membrane. Fusion of these vesicles promotes the formation of the parasitic vacuole and parasite entry. In this work, we study the requirement and the nature of SNAREs involved in the fusion events that take place during T. cruzi infection. Our results show that inhibition of N-ethylmaleimide-sensitive factor protein, a protein required for SNARE complex disassembly, impairs T. cruzi infection. Both TI-VAMP/VAMP7 and cellubrevin/VAMP3, two v-SNAREs of the endocytic and exocytic pathways, are specifically recruited to the parasitophorous vacuole membrane in a synchronized manner but, although VAMP3 is acquired earlier than VAMP7, impairment of VAMP3 by tetanus neurotoxin fails to reduce T. cruzi infection. In contrast, reduction of VAMP7 activity by expression of VAMP7's longin domain, depletion by small interfering RNA or knockout, significantly decreases T. cruzi infection susceptibility as a result of a minor acquisition of lysosomal components to the parasitic vacuole. In addition, overexpression of the VAMP7 partner Vti1b increases the infection, whereas expression of a KIF5 kinesin mutant reduces VAMP7 recruitment to vacuole and, concomitantly, T. cruzi infection. Altogether, these data support a key role of TI-VAMP/VAMP7 in the fusion events that culminate in the T. cruzi parasitophorous vacuole development.

An annotated checklist of the aquatic Adephaga (Coleoptera) of Egypt III. Noteridae, Haliplidae and Gyrinidae.

Data from previous literature were used to compile a checklist of the Egyptian fauna of families Noteridae, Haliplidae and Gyrinidae. A total of 17 species are cited for Egypt, distributed among 8 genera Neohydrocoptus Satô, 1972, Canthydrus Sharp, 1882 and Synchortus Sharp, 1880 (Noteridae); Haliplus Latreille, 1802 (Haliplidae); Dineutus MacLeay, 1825, Gyrinus Geoffroy, 1762, Orectochilus Dejean, 1833 and Orectogyrus Régimbart, 1884 (Gyrinidae). The checklist provides information for each recorded species on the type localities, type specimens, descriptors, distribution and previous published records. The checklist presented here provides a summary that can serve as the basis for future progress in the knowledge of these coleopteran families in Egypt.

Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae): Phagocytic Hemocytes in the Circulation and the Kidney.

Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy) and transmission electron microscopy (TEM). Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes) were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules) and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all) L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules). Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets') occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently) and may mean that hyalinocytes participate in the storage and circulation of this compound. Injection of microorganisms in the foot results in phagocytosis by hemocytes in the islets, and the different phagosomes formed are similar to those in circulating hyalinocytes. Dispersed hemocytes were obtained after kidney collagenase digestion and cell sorting, and they were able to phagocytize fluorescent beads. A role for the kidney as an immune barrier is proposed for this snail.

An annotated checklist of the aquatic Polyphaga (Coleoptera) of Egypt I. Family Hydraenidae.

Data from previous literature were used to compile a checklist of the Egyptian fauna of Hydraenidae (Coleoptera). The checklist includes data on the type localities, type specimens, descriptors, distributions and previous literature for 15 valid species belonging to 3 genera (Hydraena, Limnebius and Ochthebius). Ochthebius was represented by 13 species, while Hydraena and Limnebius were represented only by a single species for each of them. The present study provides a summary that can serve as the basis for future progress in the knowledge of the Egyptian Hydraenidae. 

Polyamine depletion inhibits the autophagic response modulating Trypanosoma cruzi infectivity.

Autophagy is a cell process that in normal conditions serves to recycle cytoplasmic components and aged or damaged organelles. The autophagic pathway has been implicated in many physiological and pathological situations, even during the course of infection by intracellular pathogens. Many compounds are currently used to positively or negatively modulate the autophagic response. Recently it was demonstrated that the polyamine spermidine is a physiological inducer of autophagy in eukaryotic cells. We have previously shown that the etiological agent of Chagas disease, the protozoan parasite Trypanosoma cruzi, interacts with autophagic compartments during host cell invasion and that preactivation of autophagy significantly increases host cell colonization by this parasite. In the present report we have analyzed the effect of polyamine depletion on the autophagic response of the host cell and on T. cruzi infectivity. Our data showed that depleting intracellular polyamines by inhibiting the biosynthetic enzyme ornithine decarboxylase with difluoromethylornithine (DFMO) suppressed the induction of autophagy in response to starvation or rapamycin treatment in two cell lines. This effect was associated with a decrease in the levels of LC3 and ATG5, two proteins required for autophagosome formation. As a consequence of inhibiting host cell autophagy, DFMO impaired T. cruzi colonization, indicating that polyamines and autophagy facilitate parasite infection. Thus, our results point to DFMO as a novel autophagy inhibitor. While other autophagy inhibitors such as wortmannin and 3-methyladenine are nonspecific and potentially toxic, DFMO is an FDA-approved drug that may have value in limiting autophagy and the spread of the infection in Chagas disease and possibly other pathological settings.

Multicellular spheroid formation and evolutionary conserved behaviors of apple snail hemocytes in culture.

A hemocyte primary culture system for Pomacea canaliculata in a medium mimicking hemolymphatic plasma composition was developed. Hemocytes adhered and spread onto culture dish in the first few hours after seeding but later began forming aggregates. Time-lapse video microscopy showed the dynamics of the early aggregation, with cells both entering and leaving the aggregates. During this period phagocytosis occurs and was quantified. Later (>4 h), hemocytes formed large spheroidal aggregates that increased in size and also merged with adjacent spheroids (24-96 h). Large single spheroids and spheroid aggregates detach from the bottom surface and float freely in the medium. Correlative confocal, transmission electron and phase contrast microscopy showed a peculiar organization of the spheroids, with a compact core, an intermediate zone with large extracellular lacunae and an outer zone of flattened cells; also, numerous round cells emitting cytoplasmic extensions were seen attaching to the spheroids' smooth surface. Dual DAPI/propidium iodide staining revealed the coexistence of viable and non-viable cells within aggregates, in varying proportions. DNA concentration increased during the first 24 h of culture and stabilized afterward. BrdU incorporation also indicated proliferation. Spontaneous spheroid formation in culture bears interesting parallels with spheroidal hemocyte aggregates found in vivo in P. canaliculata, and also with spheroids formed by tumoral or non-tumoral mammalian cells in vitro.

Molecular and cellular mechanisms involved in the Trypanosoma cruzi/host cell interplay.

The protozoan parasite Trypanosoma cruzi has a complex biological cycle that involves vertebrate and invertebrate hosts. In mammals, the infective trypomastigote form of this parasite can invade several cell types by exploiting phagocytic-like or nonphagocytic mechanisms depending on the class of cell involved. Morphological studies showed that when trypomastigotes contact macrophages, they induce the formation of plasma membrane protrusions that differ from the canonical phagocytosis that occurs in the case of noninfective epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle cells, the cell surface is minimally modified, suggesting the induction of a different class of process. Lysosomal-dependent or -independent T. cruzi invasion of host cells are two different models that describe the molecular and cellular events activated during parasite entry into nonphagocytic cells. In this context, we have previously shown that induction of autophagy in host cells before infection favors T. cruzi invasion. Furthermore, we demonstrate that autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi entry sites and that the newly formed T. cruzi parasitophorous vacuole has characteristics of an autophagolysosome. This review summarizes the current knowledge of the molecular and cellular mechanisms of T. cruzi invasion in nonphagocytic cells. Based on our findings, we propose a new model in which T. cruzi takes advantage of the upregulation of autophagy during starvation to increase its successful colonization of host cells.

Uric acid deposits and estivation in the invasive apple-snail, Pomacea canaliculata.

The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45 days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20 min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.

Influencia de la ingestión de grasas y la administración de estradiol en el desarrollo de carcinoma mamario inducido con DMBA en ratas / Influence of the ingestion of grease and the estradiol administration in the grow up in mamary carcinoma induce by DMBA in rats

Datos epidemiológicos sugieren que la dieta rica en grasas es un factor promotor en el desarrollo del cáncer mamario y puede esta relacionado con el estímulo estrogénico. El objetivo del presente estudio es demostrar la acción de la dieta grasa en carcinomas mamarios inducidos con 1,2-dimetilbenza(a)antraceno (DMBA) como agente promotor único o asociado con estímulo estrogénico. Se emplearon tres grupos experimentales: 1) Grupo con dieta grasa (DG) con 20 por ciento de aceite de maíz, 2) grupo con dieta normal (DN), ambos ad libitum; y 3) grupo con dieta subnormal (DSN)(10 g alimento diario). Todos con y sin estímulo estrogénico (1 *g diario de 17ß-estradiol). Al comparar los tres grupos se observó que 19 de los 21 (93 por ciento) animales con DG desarrollaron tumores mamarios, con una aparición temprana (novena semana y con el mayor tamaño (6 cm en promedio)(p=0.009). Los grupos DN Y DSN presentaron comportamiento tumoral menos agresivo, en el primer grupo la prevalencia fue de 61 por ciento con un tamaño tumoral de 5.5 cm; en el segundo la prevalencia fue de 41 por ciento, la latencia mucho mayor (aparición promedio a la semana 17) y tamaño tumoral menor (2 cm). Nuestros resultados indican que la dieta rica en grasas es un factor promotor importante e independiente del estímulo estrogénico. En general la estimulación hormonal no provocó cambios significativos en el comportamiento tumoral, aunque cabe destacar que el grupo DG con estímulo estrogénico presentó la mayor prevalencia en comparación con el resto de los grupos.

Amplificación y rearreglo in vivo del oncogen c-myc en tumores de mama humano / Entargement and read justment in vivo of the c-myc oncogene in tumors of human breast

Hemos estudiado la organozación genómica del proto-oncogen myc celular (c-myc) en 48 tumores de mama primarios de humano. Dos tipos de alteraciones (amplificación y rearreglo) se observó en 27 de los tumores estudiados (56%). El proto-oncogen c-myc, apareció amplificado de 2 a 15 veces en el DNA de 20 tumores (41%). Fragmentos relacionados a c-myc no germinal (rearreglos) de tamaño variable fueron detectados en 7 tumores de mama primarios (6 malignos, 1 benigno); 4 de estos tumores presentaron tanto arreglo como amplificación y los otros 3 presentaron únicamente rearreglo. La mayoría de los tumores analizados fueron adenocarcinomas ductal invasivo; 58% de éstos mostraron alteraciones genéticas en el locus c-myc. Aunque las alteraciones de c-myc descritas aquí no aparecen correlacionarse con el comportamiento agresivo de los tumores de mama primarios, parecen estar asociados con el desarrollo de carcinoma mamario

Alteraciones genéticas del proto-oncogen c-myc en carcinoma canalicular infiltrante de glándula mamaria y su relación con la presencia de receptores esteroideos y características microscópicas del tumor / Proto-oncogene c-myc genetic disorders in infiltrant chanalicular carcinoma of mammary gland and its relation with steroidal receptors and tumor microcopic characteristics

Se presentaron los resultados del estudio de alteraciones genéticas del proto-oncogen c-myc en 29 muestras de tumores de pacientes con carcinoma canalicular infiltrante, utilizando como referencia DNA de linfocitos de sangre periférica de las mismas pacientes. Se analizaron también las características microscópicas de los tumores estudiados y el contenido de receptores para Estradiol (E2) y Progesterona Pg) en las mismas muestras