http://hdl.handle.net/10366/3823 Investigación científica producida o editada por los departamentos y centros de la Universidad de Salamanca Fri, 15 May 2026 09:55:05 GMT 2026-05-15T09:55:05Z https://gredos.usal.es:443/bitstream/id/259208/repositorioCientifico_img.png http://hdl.handle.net/10366/3823 http://hdl.handle.net/10366/171428 [EN] It is important to determine the geological sources of Palaeolithic ambers in the south of Europe in order to understand the mobility and interchanges of prehistoric societies. Fourier transform infrared (FTIR) spectroscopy analysis carried out on Upper Palaeolithic ambers from La Garma A cave (Cantabria, Northern Spain) allowed us to identify their source area. Their diagnostic features were found to be similar to the amber obtained in the Lower Cretaceous outcrops close to this archaeological site, and to differ clearly from Baltic amber, which has been generally suggested as the amber found in European prehistoric sites. These results show that the origin of the Gravettian amber found in La Garma A is local and, consequently, a hypothetical contact route is not required to be able to account for the presence of this material in the Iberian Palaeolithic context studied here. For the first time it has been demonstrated that the provenance of an archaeological amber in the Iberian Peninsula is local, with both geographical and spectroscopical evidences. Our study also concludes that the archaeological amber of La Garma A possibly belongs to an araucariacean resin that originated from the coniferous forests which grew in the northeast portion of the Iberian Plate c.110-million years ago. Mon, 01 Jan 2007 00:00:00 GMT http://hdl.handle.net/10366/171428 2007-01-01T00:00:00Z http://hdl.handle.net/10366/171427 Las tesis despoblacionistas de Sánchez Albornoz han determinado las narrativas en torno al poblamiento de la Alta Edad Media peninsular en la cuenca del Duero, incluso después de darse por superadas. Este marco interpretativo ha sido especialmente influyente a la hora de analizar el registro material, dificultando la generación de narrativas históricas sólidas que dieran cuenta de la compleja realidad empírica. En este trabajo, se plantearán en primer lugar los principales problemas que han emergido en la interpretación arqueológica a partir de las tesis despoblacionistas. Seguidamente, a partir de una aproximación desde el concepto de localidad, se presentarán tres casos de estudio que no solo permiten superar el «desierto estratégico» del Duero, sino también asentar las bases para confrontar los diversos escenarios que se presentan una vez desechados los planteamientos basados en las dinámicas de despoblación-reconquista-repoblación. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/171427 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171426 [EN]During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of novel agents, such as new antibody-drug conjugates (ADCs). The latter are a group of drugs that benefit from the potency of cytotoxic agents whose action is specifically guided to the tumor by the target-specific antibody. Two anti-HER2 ADCs have reached the clinic: trastuzumab-emtansine and, more recently, trastuzumab-deruxtecan. In addition, several other HER2-targeted ADCs are in preclinical or clinical development, some of them with promising signs of activity. In the present review, the structure, mechanism of action, and potential resistance to all these ADCs will be described. Specific attention will be given to discussing novel strategies to circumvent resistance to ADCs. Wed, 29 Dec 2021 00:00:00 GMT http://hdl.handle.net/10366/171426 2021-12-29T00:00:00Z http://hdl.handle.net/10366/171425 [EN]Small molecule inhibitors (TKIs) of HER2 have demonstrated clinical benefit in HER2-positive breast tumors. One of them, lapatinib, is used once advanced tumors become refractory to the HER2 antibody trastuzumab. Another one, neratinib, has shown benefit in high-risk early-stage breast cancer after trastuzumab-based therapies. A common characteristic is that patients are formerly treated with trastuzumab. We have explored whether trastuzumab previous therapy affects its antitumoral action. Long time exposure of the HER2+ cell line BT474 to trastuzumab resulted in trastuzumab-insensitive cells (BTRH cells). While treatment of wild type BT474 cells with lapatinib or neratinib resulted in decreased viability, BTRH cells were resistant to the action of these TKIs. Analogous results were obtained using trastuzumab-resistant cells derived from a PDX. Functional transcriptomic analyses and biochemical studies demonstrated that the TKIs caused DNA damage and apoptosis in wild type cells, but not in BTRH. Moreover, previous treatment with trastuzumab impairs response to small TKIs, by eliminating their proapoptotic action. Moreover, actioning on the apoptotic machinery using a chemical library of proapoptotic compounds led to the identification of clinical-stage drugs that may be used to fight trastuzumab-TKI resistance. Sat, 01 Feb 2020 00:00:00 GMT http://hdl.handle.net/10366/171425 2020-02-01T00:00:00Z http://hdl.handle.net/10366/171424 [EN]Ocoxin Oral Solution (OOS) and Viusid (VS) are nutritional supplements that include several natural products which affect different cellular functions, such as proliferation or the redox status. In addition, some of their constituent components have been described to exert an antiviral effect. Considering this, it was hypothesized that treatment with OOS and VS could protect from viral infections. In order to evaluate the impact of OOS and VS on viral infection, lentivirus and retrovirus whose genomes coded for green fluorescent protein were used. In addition, and as a second approach to measure viral infection, a hemagglutinin-tagged form of the mitogen-activated protein kinase ERK5 was also inserted in the retroviral vector. Viral particles produced in 293T cells were used to infect HeLa cells in the presence or absence of OOS or VS. It was observed that VS had a minimal effect on the capacity of either lentivirus or retrovirus to infect HeLa cells. However, OOS significantly reduced the infection of HeLa cells with both of these viruses. The effect was dose-dependent, reaching a maximum at a 1:100 dilution of OOS. These results suggested that, in addition to its well-known antitumoral properties, OOS may also inhibit infection with viruses. This effect is relevant since patients receiving oncological therapies are more susceptible to viral infections, and nutritional supplements such as OOS may help in reducing the severity of these potential pathogenic infections. Fri, 01 Oct 2021 00:00:00 GMT http://hdl.handle.net/10366/171424 2021-10-01T00:00:00Z http://hdl.handle.net/10366/171423 [ES]Publicación colectiva que reúne los casos clínicos presentados al 16º Concurso SEOM de casos clínicos de 2023, estructurados por bloques temáticos como biología molecular y tumores germinales, entre otros. El volumen compila experiencias clínicas complejas, procesos diagnósticos, decisiones terapéuticas y bibliografía de apoyo, con finalidad de actualización y formación para profesionales de la oncología. Sun, 01 Jan 2023 00:00:00 GMT http://hdl.handle.net/10366/171423 2023-01-01T00:00:00Z http://hdl.handle.net/10366/171420 [EN]Ocoxin Oral Solution (OOS) is a nutritional supplement whose formulation includes several plant extracts and natural products with demonstrated antitumoral properties. This review summarizes the antitumoral action of the different constituents of OOS. The action of this formulation on different preclinical models as well as clinical trials is reviewed, paying special attention to the mechanism of action and quality of life improvement properties of this nutritional supplement. Molecularly, its mode of action includes a double edge role on tumor biology, that involves a slowdown in cell proliferation accompanied by cell death induction. Given the safety and good tolerability of OOS, and its potentiation of the antitumoral effect of other standard of care drugs, OOS may be used in the oncology clinic in combination with conventional therapies. Mon, 31 Aug 2020 00:00:00 GMT http://hdl.handle.net/10366/171420 2020-08-31T00:00:00Z http://hdl.handle.net/10366/171419 [ES]Publicación colectiva que reúne los casos clínicos presentados al 18º Concurso SEOM de casos clínicos de 2025, estructurados por bloques temáticos como biología molecular y tumores germinales, entre otros. El volumen compila experiencias clínicas complejas, procesos diagnósticos, decisiones terapéuticas y bibliografía de apoyo, con finalidad de actualización y formación para profesionales de la oncología. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/171419 2025-01-01T00:00:00Z http://hdl.handle.net/10366/171418 [EN]Acquired brain injuries have an important impact on the whole family system. Families may need support and specific intervention addressing their needs. Currently, there is no available validated instruments that assess Family Quality of Life in this population in Spain. Thus, the objective of this study is to examine psychometric properties of the new Family Quality of Life Scale – Acquired Brain Injury (FQoLS- ABI) in this country. A total of 231 people who belonged to families of individuals with ABI took part in the study (Gender: 71% women; Age: M=55.8, SD=12.6). A pilot version with 71 items of the FQoLS-ABI was applied. For each domain, item properties, confirmatory factor analyses, internal consistency, and Graded Response Model (GRM) of Semejima (1969) were examined. The field-test version was reduced to 35 items with adequate fit indices (CFI = .981-.996; TLI = .970-.993; RMSEA = .050-.087; SRMR = .022-.040) and internal consistency indices (Cronbach’s α = .77- .88; McDonalds’ ω = .77-.88; Guttman’s λ-2= .78-.88). According to GRM, item discrimination parameters were moderate to very high (α i = .71-3.48), as well as the five domains provided informative measurement across the wide range of FQoL levels, making the scale particularly useful for identifying families with low to moderate levels of FQoL. The FQoLS-ABI is a valid and reliable instrument. It is a useful tool for clinical and research contexts for identifying support needs of families of individuals with ABI. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/171418 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171410 [EN] Experimental evidence indicates that a high seizure burden can induce cerebral overexpression of P-glycoprotein (P-gp) at the blood–brain barrier, a phenomenon associated with drug-resistant epilepsy under the “transporter hypothesis”, but also at the neuronal level, linked to a reduced seizure threshold, increased seizure severity (SS), status epilepticus (SE), and a high spontaneous death (SD) rate. In contrast, we recently described a progressive reduction in SS and the absence of SE and SD in GASH/Sal hamsters subjected to 45 audiogenic seizures. Here, we examined SS, SE, and the SD, and the expression of P-gp, erythropoietin receptor (EPO-R), hypoxia-inducible factor 1 alpha subunit (HIF-1α) and cyclooxygenase 2 (COX-2), in the brains of GASH/Sal hamsters following 20 audiogenic kindling stimulations (AUK-20). SS was evaluated using the midbrain and limbic severity scales; gene expression was assessed by RT-qPCR and P-gp protein levels were measured by immunohistochemistry and Western blot (IHC/WB) analysis. A modest decrease in midbrain SS was observed, without an increase in the already low limbic SS scores, and no SE or SD events occurred. P-gp levels remained low in both IHC and WB analyses. At the mRNA level, we detected increased EPO-R expression, decreased HIF-1α, and increased COX-2 without an accompanying increased in Abcb1b. Unlike findings from other experimental epilepsy models, AUK-20 in GASH/Sal hamsters does not enhance limbic SS, trigger SE or SD, or induce P-gp overexpression in the brain. Independently of the implications for drug resistance, the lack of cerebral P-gp overexpression without increased SS in the AUK-20-GASH/Sal model supports a potential role of P-gp in modulating seizure severity and epilepsy-associated mortality risk. Thu, 09 Apr 2026 00:00:00 GMT http://hdl.handle.net/10366/171410 2026-04-09T00:00:00Z http://hdl.handle.net/10366/171408 [ES] Análisis de los objetos de adorno del Paleolítico y Mesolítico en los yacimientos arqueológicos europeos Sun, 01 Jan 2006 00:00:00 GMT http://hdl.handle.net/10366/171408 2006-01-01T00:00:00Z http://hdl.handle.net/10366/171407 [ES] En este artículo trataremos de exponer la historiografía relativa al estudio de los objetos de adorno-colgantes en Europa, poniendo un énfasis especial en las investigaciones llevadas a cabo de estos materiales arqueológicos en la Cornisa Cantábrica y en el Valle del Ebro. Sun, 01 Jan 2006 00:00:00 GMT http://hdl.handle.net/10366/171407 2006-01-01T00:00:00Z http://hdl.handle.net/10366/171406 [ES] Se exponen los 13 yacimientos prehistóricos de la Cornisa Cantábrica (norte de España), con edades desde el Paleolítico superior hasta la Edad del Bronce, con presencia de ámbar. Se ha estudiado el origen geográfico de este ámbar por las implicaciones de los resultados en el conocimiento de aspectos culturales y comerciales de las sociedades prehistóricas. Se ha investigado si la procedencia del ámbar pudo ser local, con origen en los aflorarniencos naturales de ámbar del Cretácico de la Cornisa Cantábrica, o fue alóctona, de la región del Báltico en el norte de Europa. Para ello se ha realizado iina comparación de la localización geográfica de los yacimientos arqueológicos y paleontológicos, y de los espectros de infrarrojos (IRTF) de ambos tipos de ámbarcs para algunos de los yacimientos. El ámbar del Crecácico de España posee caracteristicas gemológicas, que lo convierten en una materia prima adecuada para la elaboración de objetos de adorno con instrumental Iítico. El estudio concluye que el ámbar arqiieológico prehistórico de la Cornisa Cantábrica tuvo en general un origen local, y que probablemente era obtenido en áreas fuente naturales muy cercanas a los yacimientos arqueológicos prehistóricos. Los espectros de infrarrojos (IRTF) de los ámbares de los yacimientos en cueva de El Pendo, Morín, LI Garma A y el monumento megalítico de Trikuaizti 1 muestran que corresponden a ámbares cretácicos. Se han limitado cuatro áreas en las que existe una relación espacial entre los yacimientos arqueológicos y paleontológicos con ámbar y se proponen como hipotéricas zonas de aprovisionamiento y LISO de ámbar cretácico en la Prehistoria de la Cornisa Cantábrica. Según muestran los análisis, únicamente el ámbar del monumento megalítico de Larrarte corresponde a succinita del Terciario del Báltico. Estos datos indican que durante el Megalítico, al menos en una pequeña área de la provincia de Guipúzcoa (yacimientos de Trikuaizci 1 y Larrarte), los grupos humanos utilizaron tanto el ámbar autóctono como el alóctono Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/171406 2025-01-01T00:00:00Z http://hdl.handle.net/10366/171405 [EN] This paper presents an overview of the use of Proboscidean remains in every day Palaeolithic life, in an attempt to illuminate some aspects of the relationship between Proboscideans and humans during the Palaeolithic from an archaeological perspective. A short survey of the evidence is given, focussing on the associations of lithic tools and Proboscidean remains and the utilisation of Proboscidean remains to produce bone tools, objects of art and personal decoration and dwellings. The evidence is compiled and general trends in the archaeological record are outlined Sat, 01 Jan 2005 00:00:00 GMT http://hdl.handle.net/10366/171405 2005-01-01T00:00:00Z http://hdl.handle.net/10366/171404 [EN]Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ibα-IX-V (GPIbα-IX-V) complex and mature β1 integrin, and increased apoptosis. In vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIbα and β1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function. Thu, 26 Jan 2023 00:00:00 GMT http://hdl.handle.net/10366/171404 2023-01-26T00:00:00Z http://hdl.handle.net/10366/171403 [EN]Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management. Wed, 01 Feb 2023 00:00:00 GMT http://hdl.handle.net/10366/171403 2023-02-01T00:00:00Z