Sílabo de Finanzas I

El curso de Finanzas I es de naturaleza aplicativa y se propone desarrollar en los estudiantes la competencia para explicar y aplicar los principios y los modelos de la Teoría Financiera en la gestión financiera de una empresa con el objetivo de maximizar el valor de la empresa. El curso sirve de base para los cursos de Finanzas II ,Presupuestos, Contabilidad Gerencial y Formulación y Evaluación de Proyectos

Repression of embryonic genome: how, why?

L’expression du génome de l’embryon a été étudiée en utilisant des lapins dont la lignée germinale a été enrichie avec un gène marqueur associé au promoteur du gène tk du virus de l’herpès, et à des séquences régula trices dérivées d’introns et d’exons du gène humain hprtet de la séquence F101 du polyome. Cette construction, nommée UPytl2LacZ, s’exprime dans les cellules de l’embryon transgénique collecté au stade une cellule et maintenu en culture. Lorsqu’il est d’origine paternelle, le transgène ne s’exprime in vitro qu’à partir du stade 8 cellules alors que d’origine maternelle il s’exprime à partir du stade 16 cellules. Ainsi, in vitro, l’expression du génome est réprimée pendant les premiers stades de développement de l’embryon de lapin. La répression du génome d’origine maternelle a une durée plus longue que celle du génome d’origine paternelle ; la différence correspond au temps nécessaire à la réalisation un cycle cellulaire supplémentaire. La présence d’aphidicoline, un inhibiteur de synthèse de l’ADN, dès le début de la culture s’oppose au passage de l’embryon du stade 2 au stade 4 cellules. Dans ces conditions, le transgène n’est plus exprimé quelle que soit l’origine germinale du gène. L’addition plus tardive de l’aphidicoline dans le milieu de culture, qui permet d’arrêter le développement de l’embryon au stade 4 cellules, réduit encore significativement l’expression du génome d’origine paternelle ou maternelle. Ces résultats montrent que la transcription devient possible seulement après la réalisation des phases de synthèse de l’ADN, ce qui suggère qu’une réoganisation fonctionnelle du génome de l’embryon est nécessaire pour la levée de la répression de la transcription

RACK1, a clue to the diagnosis of cutaneous melanomas in horses

Abstract Background Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Results Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features. Conclusions This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine.</p

RACK1, a clue to the diagnosis of cutaneous melanomas in horses

Chantier qualité GAInternational audienceBackgroundMelanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses.ResultsUsing immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features.ConclusionsThis study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations.</p> <p>Results</p> <p>We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including <it>GNB2L1 </it>which was found upregulated in the melanoma library. <it>In situ </it>hybridisation confirmed <it>GNB2L1 </it>overexpression in MeLiM melanocytic lesions. <it>GNB2L1 </it>encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low.</p> <p>Conclusion</p> <p>RACK1 overexpression detected <it>in situ </it>in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to progress in diagnosis.</p

Canine melanoma diagnosis: RACK1 as a potential biological marker

Chantier qualité GAInternational audienceMelanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation-3

D) Melanoma metastasis in a lymph node (B), lung (C) and heart (D). Three dimensional 'orthogonal' slice projection analyses are presented as in Figure 3. Nuclei are shown in blue. (A1) Transmission photograph corresponding to (A2). (A3) Zoom on (A2) inset. White arrowheads in (A1-A3) point at a dermal cutaneous melanoma cell positive for MITF and analysed by orthogonal projection. Note the comparable RACK1 cytosolic signal on dermal melanoma cells and epidermal keratinocytes. High levels of RACK1 are seen in cutaneous and metastatic melanoma cells with perinuclear localization. Furthermore, in metastases, RACK1 is seen within the nuclei, as indicated by yellow arrowheads on the optical slice and the orthogonal projections. Dotted lines in (A1) and (A2) indicate epidermis-dermis boundaries. e, epidermis; d, dermis. Bar = 5 μm.<p><b>Copyright information:</b></p><p>Taken from "Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation"</p><p>http://www.molecular-cancer.com/content/7/1/34</p><p>Molecular Cancer 2008;7():34-34.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2387171.</p><p></p

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation-6

(red fluorescence). (C, D) Confocal microscopy analysis of double labelling of RACK1 protein (green fluorescence, biotin amplified signal), with phospho-PKCαβ (red fluorescence). (A, C) Nevi. (B, D) Melanoma metastasis in lymph node. High levels of activated PKC are seen on MITF-positive melanoma cells in metastasis compared to MITF-positive melanocytes in nevus (arrowheads in B and A, respectively). Dermal melanocytes in nevus display low cytoplasmic RACK1 and nuclear phospho-PKC signals (arrow in C). Abundant signals for RACK1 and activated PKCαβ partially colocalise (arrow in D). Nuclear counterstaining is shown in blue. Dotted line indicates epidermis-dermis boundary. e, epidermis; d, dermis. Bar = 10 μm.<p><b>Copyright information:</b></p><p>Taken from "Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation"</p><p>http://www.molecular-cancer.com/content/7/1/34</p><p>Molecular Cancer 2008;7():34-34.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2387171.</p><p></p

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation-0

displayed on the left (skin, lung, liver and lymph node) and tumoral (T) tissues on the right (cutaneous melanoma, metastatic melanoma from lung, liver and lymph node). Note the intense signal on the tumors compared to the healthy or non-compromised tissues, with the antisense probe, except for lymph node. (C) Darkfield photomicrograph taken from a MeLiM melanoma lung metastasis hybridised with the antisense probe. (D) Consecutive section stained with hematoxylin and eosin. The pigmented area in the tumor matches the region which exhibits silver grains on (C). Bar = 1 cm for A and B and 100 μm for C and D.<p><b>Copyright information:</b></p><p>Taken from "Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation"</p><p>http://www.molecular-cancer.com/content/7/1/34</p><p>Molecular Cancer 2008;7():34-34.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2387171.</p><p></p

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation-5

Tasis in lymph node. (C, D) Melanoma metastasis in liver. High levels of RACK1 are seen in the cytoplasm of all metastatic human melanocytes. Sections are from 4 different patients. Nuclear counterstaining is shown in blue in D. Bar = 10 μm.<p><b>Copyright information:</b></p><p>Taken from "Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation"</p><p>http://www.molecular-cancer.com/content/7/1/34</p><p>Molecular Cancer 2008;7():34-34.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2387171.</p><p></p