http://hdl.handle.net/10171/12201 2013-05-22T20:32:39Z 2013-05-22T20:32:39Z Vega, F. (Francisco) Errasti, P. (Pedro) Pardo-Mindan, F.J. (Francisco Javier) http://hdl.handle.net/10171/23411 2012-10-19T00:05:01Z 1996-12-31T23:00:00Z

Title: Renal transplantation from a donor with a nail–patella syndrome Author(s) : Vega, F. (Francisco); Errasti, P. (Pedro); Pardo-Mindan, F.J. (Francisco Javier)

1996-12-31T23:00:00Z Pardo-Mindan, F.J. (Francisco Javier) Guillen, F.J. (F. J.) Villas, C. (Carlos) Vazquez, J.J. (Jesús Jaime) http://hdl.handle.net/10171/23409 2012-10-19T00:10:40Z 1980-12-31T23:00:00Z

Title: A Comparative Ultrastructural Study of Chondrosarcoma, Chordoid Sarcoma, and Chordoma Author(s) : Pardo-Mindan, F.J. (Francisco Javier); Guillen, F.J. (F. J.); Villas, C. (Carlos); Vazquez, J.J. (Jesús Jaime) Abstract: A morphologic and electron microscopic study was made of two chordoid sarcomas. These lesions were compared with two classical chondrosarcomas and two chordomas. These chondrosarcoma cells showed many features common to chondrocytes, such as abundant RER, well-developed Golgi complexes, and microvillous cytoplasmatic membranes. The chordoid sarcomas bore a close morphologic resemblance to the chordomas but the ultrastructural features revealed a close relationship to the chondrosarcomas. The chordoid sarcoma and chondrosarcoma cells had scalloped cytoplasmatic membranes, variable amounts of glycogen, round or oval nuclei and microfibrils, collagen, and electron-dense granules in the ground substance. The chordoma was characterized by the presence of stellate and physalipherous cells, as well as many transitional cells, with varying nuclear morphology; dilated and irregular RER in contact with mitochondria and morphologically varied vacuoles are the main features in the cytoplasm. This study suggests that chordoid sarcoma represents a variety of the chondrosarcoma rather than a form of chordoma. These findings also support the suggestion of Weiss that chordoid sarcoma is an extraskeletal myxoid chondrosarcoma

1980-12-31T23:00:00Z Alava, E. (Enrique) de Panizo, A. (Ángel) Antonescu, C.R. (Cristina R.) Huvos, A.G. (Andrew G.) Pardo-Mindan, F.J. (Francisco Javier) Barr, F.G. (Frederic G.) Ladanyi, M. (Marc) http://hdl.handle.net/10171/23392 2012-10-17T00:09:44Z 1999-12-31T23:00:00Z

Title: Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma Author(s) : Alava, E. (Enrique) de; Panizo, A. (Ángel); Antonescu, C.R. (Cristina R.); Huvos, A.G. (Andrew G.); Pardo-Mindan, F.J. (Francisco Javier); Barr, F.G. (Frederic G.); Ladanyi, M. (Marc) Abstract: The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway.

1999-12-31T23:00:00Z Frühbeck, G. (Gema) Gomez-Ambrosi, J. (Javier) Muruzabal, F.J. (Francisco José) Burrell, M.A. (M.A.) http://hdl.handle.net/10171/23359 2012-10-16T00:09:30Z 2000-12-31T23:00:00Z

Title: The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation Author(s) : Frühbeck, G. (Gema); Gomez-Ambrosi, J. (Javier); Muruzabal, F.J. (Francisco José); Burrell, M.A. (M.A.) Abstract: The ability to ensure continuous availability of energy despite highly variable supplies in the environment is a major determinant of the survival of all species. In higher organisms, including mammals, the capacity to efficiently store excess energy as triglycerides in adipocytes, from which stored energy could be rapidly released for use at other sites, was developed. To orchestrate the processes of energy storage and release, highly integrated systems operating on several physiological levels have evolved. The adipocyte is no longer considered a passive bystander, because fat cells actively secrete many members of the cytokine family, such as leptin, tumor necrosis factor-alpha, and interleukin-6, among other cytokine signals, which influence peripheral fuel storage, mobilization, and combustion, as well as energy homeostasis. The existence of a network of adipose tissue signaling pathways, arranged in a hierarchical fashion, constitutes a metabolic repertoire that enables the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess.

2000-12-31T23:00:00Z Obeso, J.A. (José A.) Rodriguez-Oroz, M.C. (María Cruz) Lanciego, J. (J.L.) Rodriguez-Diaz, M. (Manuel) http://hdl.handle.net/10171/20337 2011-12-21T08:59:05Z 2003-12-31T23:00:00Z

Title: How does Parkinson's disease begin? The role of compensatory mechanisms Author(s) : Obeso, J.A. (José A.); Rodriguez-Oroz, M.C. (María Cruz); Lanciego, J. (J.L.); Rodriguez-Diaz, M. (Manuel)

2003-12-31T23:00:00Z Rouzaut, A. (Ana) Irigoyen, M. (Marta) Montuenga, L.M. (Luis M.) http://hdl.handle.net/10171/20315 2012-08-07T06:32:33Z 2006-12-31T23:00:00Z

Title: Lymphangiogenesis and lung cancer Author(s) : Rouzaut, A. (Ana); Irigoyen, M. (Marta); Montuenga, L.M. (Luis M.)

2006-12-31T23:00:00Z Jimenez, N. (Nuria) Jongsma, J. (Johan) Calvo, A. (Alfonso) Kwast, T.H. (Theodorus H. ) van der Treston, A.M. (Anthony M.) Cuttitta, F. (Frank) Schröder, F.H. (Fritz H.) Montuenga, L.M. (Luis M.) Steenbrugge, G.J. (Gert J.) van http://hdl.handle.net/10171/20190 2012-01-14T18:56:59Z 2000-12-31T23:00:00Z

Title: Peptidylglycine alpha-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate Author(s) : Jimenez, N. (Nuria); Jongsma, J. (Johan); Calvo, A. (Alfonso); Kwast, T.H. (Theodorus H. ) van der; Treston, A.M. (Anthony M.); Cuttitta, F. (Frank); Schröder, F.H. (Fritz H.); Montuenga, L.M. (Luis M.); Steenbrugge, G.J. (Gert J.) van Abstract: Most PCs show NE differentiation. Several studies have tried to correlate NE expression with disease status, but the reported findings have been contradictory. Prostatic NE cells synthesize peptides with a wide spectrum of potential functions. Some of these active peptides, such as PAMP, are amidated. PAM is the only carboxy-terminal peptide-amidating enzyme identified. We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior androgen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds. Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach statistical significance, PAMP- or PAM-immunoreactive cells were induced after androgen-blockade therapy. In the PC-310 and PC-295 androgen-dependent models, PAMP or PAM NE differentiation was induced after castration in different ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation. We show induction of expression of 2 new NE markers in clinical specimens and xenografted PC after endocrine therapy.

2000-12-31T23:00:00Z Jordana, R. (Rafael) Baquero, E. (Enrique) Montuenga, L.M. (Luis M.) http://hdl.handle.net/10171/20189 2013-03-02T01:09:38Z 1999-12-31T23:00:00Z

Title: A new type of arthropod photoreceptor Author(s) : Jordana, R. (Rafael); Baquero, E. (Enrique); Montuenga, L.M. (Luis M.) Abstract: A new type of photoreceptor for the phylum Arthropoda, found in the class Collembola (Arthropoda, Hexapoda) is reported. This new light-sensitive structure consists of a pair of interocular vesicles present in the genus Vesicephalus Richards, 1964 and is anatomically related to the cluster of ommatidia. The absence of a lens, the presence of a rabdome in the upper part of the vesicle and the reflection and refraction of light by a hemolymph bubble with incidence to the rhabdomeric structure are the main traits of this new photoreceptor.

1999-12-31T23:00:00Z Elizegi, E. (E.) Pino, I. (Irene) Vicent, S. (Silvestre) Blanco, D. (D.) Saffiotti, U. (Umberto) Montuenga, L.M. (Luis M.) http://hdl.handle.net/10171/20188 2012-01-14T18:56:59Z 2000-12-31T23:00:00Z

Title: Hyperplasia of alveolar neuroendocrine cells in rat lung carcinogenesis by silica with selective expression of proadrenomedullin-derived peptides and amidating enzymes Author(s) : Elizegi, E. (E.); Pino, I. (Irene); Vicent, S. (Silvestre); Blanco, D. (D.); Saffiotti, U. (Umberto); Montuenga, L.M. (Luis M.) Abstract: Pulmonary neuroendocrine (NE) cells are found as clusters called neuroepithelial bodies (NEBs) or as single cells scattered in the respiratory epithelium. They express a variety of bioactive peptides, and they are thought to be the origin of NE lung tumors. Proadrenomedullin N-terminal 20 peptide (PAMP) is a peptide derived from the same precursor as adrenomedullin (AM). AM and PAMP are C-terminally amidated during their processing by a well-characterized amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). We explored AM, PAMP, and PAM expression as markers for NE hyperplasia in three rodent species (Fischer 344 rats, Syrian golden hamsters, and A/J mice) after a single intratracheal instillation of crystalline silica (quartz), which was previously found to induce different reactions in the three species. Rats developed a marked silicosis, with alveolar and bronchiolar hyperplasia and formation of peripheral lung epithelial tumors. Mice developed a moderate degree of silicosis, but not epithelial hyperplasia or tumors. Hamsters showed dust-storage lesions, but not silicosis or tumors. NE cells were immunolabeled for calcitonin gene-related peptide (CGRP), AM, PAMP, and PAM in serial sections of each lung. The numbers of positive NEBs per lung area and positive cells per NEB were quantified. A marked hyperplastic reaction in the NEBs of silica treated rats occurred only in alveolar NEBs, but not in bronchiolar NEBs. From Month 11 onwards, there were marked differences in the number of alveolar NEBs per section and in the number of cells per alveolar NEB immunoreactive for CGRP. No hyperplastic NE cell reaction was observed in silica-treated mice and hamsters. Significant PAMP and PAM expression was seen only in rat hyperplastic alveolar and in bronchiolar NEBs from Month 11 onwards. In E18, rat fetal lung NEBs were found to be strongly positive for PAMP and PAM.

2000-12-31T23:00:00Z Garayoa, M. (Mercedes) Bodegas, M.E. (M.E.) Cuttitta, F. (Frank) Montuenga, L.M. (Luis M.) http://hdl.handle.net/10171/20187 2012-01-14T18:56:59Z 2001-12-31T23:00:00Z

Title: Adrenomedullin in mammalian embryogenesis Author(s) : Garayoa, M. (Mercedes); Bodegas, M.E. (M.E.); Cuttitta, F. (Frank); Montuenga, L.M. (Luis M.) Abstract: Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

2001-12-31T23:00:00Z Calvo, A. (Alfonso) Abasolo, I. (Ibane) Jimenez, N. (Nuria) Wang, Z. (Zhou) Montuenga, L.M. (Luis M.) http://hdl.handle.net/10171/20186 2012-01-14T18:56:58Z 2001-12-31T23:00:00Z

Title: Adrenomedullin and proadrenomedullin N-terminal 20 peptide in the normal prostate and in prostate carcinoma Author(s) : Calvo, A. (Alfonso); Abasolo, I. (Ibane); Jimenez, N. (Nuria); Wang, Z. (Zhou); Montuenga, L.M. (Luis M.) Abstract: There is increasing evidence for the important role played by regulatory peptides in the physiology of the normal and neoplastic prostate. Adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP) are recently discovered regulatory peptides widely expressed in the normal prostate and in prostate carcinoma. AM is produced in secretory, stroma, and endothelial cells and in neurons of the prostate ganglia. PAMP is only produced by neuroendocrine cells. The expression of AM mRNA is regulated by androgens in the rat prostate. The number of neuroendocrine cells expressing PAMP is increased in prostate carcinoma after androgen deprivation, which shows that this peptide could regulate androgen-independent prostate tumor growth. However, the roles of AM and PAMP in the normal prostate and in prostate carcinoma are yet to be elucidated.

2001-12-31T23:00:00Z Field, J. (J. K.) Brambilla, C. (C.) Caporaso, N. (N.) Flahault, A. (A.) Henschke, C.I. (C.I.) Herman, J. (J.) Hirsch, F. (F.) Lachmann, P. (P.) Lam, S. (S.) Maier, S. (S.) Montuenga, L.M. (Luis M.) Mulshine, J.L. (James L.) Murphy, M. (Murphy) Pullen, J. (J.) Spitz, M. (M.) Tockman, M. (M.) Tyndale, R. (R.) Wistuba, I.I. (Ignacio I.) Youngson, J. (J.) http://hdl.handle.net/10171/20184 2012-01-14T18:56:58Z 2001-12-31T23:00:00Z

Title: Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations Author(s) : Field, J. (J. K.); Brambilla, C. (C.); Caporaso, N. (N.); Flahault, A. (A.); Henschke, C.I. (C.I.); Herman, J. (J.); Hirsch, F. (F.); Lachmann, P. (P.); Lam, S. (S.); Maier, S. (S.); Montuenga, L.M. (Luis M.); Mulshine, J.L. (James L.); Murphy, M. (Murphy); Pullen, J. (J.); Spitz, M. (M.); Tockman, M. (M.); Tyndale, R. (R.); Wistuba, I.I. (Ignacio I.); Youngson, J. (J.) Abstract: The Second Molecular Biomarkers Workshop was held at the Roy Castle International Centre for Lung Cancer Research in Liverpool, in June 2001 and it brought together experts in the clinical, epidemiological and molecular-pathology of lung cancer from Europe and the USA, to address issues surrounding the development of a European strategy for early lung cancer detection. The 2001 Workshop Breakout Groups concentrated on the current challenges in the early detection of lung cancer which need to be addressed in the light of the recent surge in interest in many countries for mounting new clinical trials to evaluate the utility of Spiral CT in early lung cancer detection. If population-based trials of CT screening are mounted it will also be a favorable clinical environment in which to evaluate efficiently recent advances in molecular screening and genotyping. The Workshop focused specifically on: a) clinical and molecular biomarkers, b) sputum as an early detection and diagnostic tool, c) validation of molecular markers prior to their use in early detection trials and d) ethical issues that have to be considered in early lung cancer detection trials. A distillation of the Workshop discussions is given in this article.

2001-12-31T23:00:00Z Manzano, R.G. (Ramón G.) Montuenga, L.M. (Luis M.) Dayton, M. (M.) Dent, P. (P.) Kinoshita, I.(Ichiro) Vicent, S. (Silvestre) Gardner, G.J. (Ginger J.) Nguyen, P. (PhuongMai) Choi, Y.H. (Yung-Hyun) Trepel, J. (Jane) Auersperg, N. (N.) Birrer, M.J. (Michael J.) http://hdl.handle.net/10171/20183 2012-01-14T18:56:57Z 2001-12-31T23:00:00Z

Title: CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential Author(s) : Manzano, R.G. (Ramón G.); Montuenga, L.M. (Luis M.); Dayton, M. (M.); Dent, P. (P.); Kinoshita, I.(Ichiro); Vicent, S. (Silvestre); Gardner, G.J. (Ginger J.); Nguyen, P. (PhuongMai); Choi, Y.H. (Yung-Hyun); Trepel, J. (Jane); Auersperg, N. (N.); Birrer, M.J. (Michael J.) Abstract: Although early stage ovarian cancer can be effectively treated with surgery and chemotherapy, the majority of cases present with advanced disease, which remains essentially incurable. Unfortunately, little is known about the genes important for the development and progression of this disease. In this study, the expression of 68 phosphatases was determined in immortalized ovarian epithelial cells (IOSE) and compared to ovarian cancer cell lines. CL100, a dual specificity phosphatase, displayed 10-25-fold higher expression in normal compared to malignant ovarian cell lines. Immunohistochemical staining of normal ovaries and 68 ovarian cancer specimens confirmed this differential expression. Re-expression of CL100 in ovarian cancer cells decreased adherent and non-adherent cell growth and induced phenotypic changes including loss of filopodia and lamellipodia with an associated decrease in cell motility. Induced expression of CL100 in ovarian cancer cells suppressed intraperitoneal tumor growth in nude mice. These results show for the first time that CL100 expression is altered in human ovarian cancer, that CL100 expression changes cell morphology and motility, and that it suppresses intraperitoneal growth of human ovarian epithelial cancer. These data suggest that down-regulation of CL100 may play a role in the progression of human ovarian cancer.

2001-12-31T23:00:00Z Cuttitta, F. (Frank) Pio, R. (Rubén) Garayoa, M. (Mercedes) Zudaire, E. (Enrique) Julian, M. (Miguel) Elssasser, T. (T.) Montuenga, L.M. (Luis M.) Martinez, A. (Alfredo) http://hdl.handle.net/10171/20182 2012-01-14T18:57:09Z 2001-12-31T23:00:00Z

Title: Adrenomedullin functions as an important tumor survival factor in human carcinogenesis Author(s) : Cuttitta, F. (Frank); Pio, R. (Rubén); Garayoa, M. (Mercedes); Zudaire, E. (Enrique); Julian, M. (Miguel); Elssasser, T. (T.); Montuenga, L.M. (Luis M.); Martinez, A. (Alfredo) Abstract: Adrenomedullin (AM) is a pluripotent regulatory peptide initially isolated from a human pheochromocytoma (adrenal tumor) and subsequently shown to play a critical role in cancer cell division, tumor neovascularization, and circumvention of programmed cell death, thus it is an important tumor cell survival factor underlying human carcinogenesis. A variety of neural and epithelial cancers have been shown to produce abundant amounts of AM. Recent findings have implicated elevation of serum AM with the onset of malignant expression. In addition, patients with tumors producing high levels of this peptide have a poor prognostic clinical outcome. Given that most human epithelial cancers display a microenvironment of reduced oxygen tension, it is interesting to note that AM and several of its receptors are upregulated during hypoxic insult. The existence of such a regulatory pathway has been implicated as the basis for the overexpression of AM/AM-R in human malignancies, thereby generating a subsequent autocrine/paracrine growth advantage for the tumor cell. Furthermore, AM has been implicated as a potential immune suppressor substance, inhibiting macrophage function and acting as a newly identified negative regulator of the complement cascade, protective properties which may help cancer cells to circumvent immune surveillance. Hence, AM's traditional participation in normal physiology (cited elsewhere in this issue) can be extended to a primary player in human carcinogenesis and may have clinical relevance as a biological target for the intervention of tumor progression.

2001-12-31T23:00:00Z Montuenga, L.M. (Luis M.) Guembe, L. (L.) Burrell, M.A. (M.A.) Bodegas, M.E. (M.E.) Calvo, A. (Alfonso) Sola, J.J. (Jesús J.) Sesma, M.P. (María Pilar) Villaro, A.C. (Ana Cristina) http://hdl.handle.net/10171/20181 2012-01-14T18:56:57Z 2002-12-31T23:00:00Z

Title: The diffuse endocrine system: from embryogenesis to carcinogenesis Author(s) : Montuenga, L.M. (Luis M.); Guembe, L. (L.); Burrell, M.A. (M.A.); Bodegas, M.E. (M.E.); Calvo, A. (Alfonso); Sola, J.J. (Jesús J.); Sesma, M.P. (María Pilar); Villaro, A.C. (Ana Cristina) Abstract: In the present review we will summarise the current knowledge about the cells comprising the Diffuse Endocrine System (DES) in mammalian organs. We will describe the morphological, histochemical and functional traits of these cells in three major systems gastrointestinal, respiratory and prostatic. We will also focus on some aspects of their ontogeny and differentiation, as well as to their relevance in carcinogenesis, especially in neuroendocrine tumors. The first chapter describes the characteristics of DES cells and some of their specific biological and biochemical traits. The second chapter deals with DES in the gastrointestinal organs, with special reference to the new data on the differentiation mechanisms that leads to the appearance of endocrine cells from an undifferentiated stem cell. The third chapter is devoted to DES of the respiratory system and some aspects of its biological role, both, during development and adulthood. Neuroendocrine hyperplasia and neuroendocrine lung tumors are also addressed. Finally, the last chapter deals with the prostatic DES, discussing its probable functional role and its relevance in hormone-resistant prostatic carcinomas.

2002-12-31T23:00:00Z