Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer

Conflicts of Interest: AFD declares travel expenses from Roche, MSD and Novartis. EF declares a consulting and advisory role for Novartis; research funding from Pfizer and travel expenses from Lilly, Novartis and Pfizer. AP declares travel expenses from Roche and BMS. MM has participated as an advisor of Lilly, Seagen, Novartis, Pficer, Roche, and Kern; her institution has received re- search funding from Pfizer, Roche, Eisai, Astrazeneca and Kern and travel expenses from Gilead. MB declares no potential conflict of interest.Funding: This research received no external funding. EF is supported by a Rio Hortega grant from the Instituto de Salud Carlos III (ISCIII- CM20/00027).Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T- DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investi-gated in this setting, with promising but controversial results obtained to date

Diagenetic processes in a partially dolomitized carbonate reservoir : Casablanca oil field, Mediterranean Sea, offshore Spain

Mesozoic and Neogene carbonates located in the Valencia Trough (offshore Spain, western Mediterranean Sea) are oil reservoirs. This paper investigates the diagenetic evolution of the Upper Jurassic limestones, currently dolomitized, that constitute the main reservoir of the Casablanca oil field. Core samples from Casablanca-1A well have been studied to determine the diagenetic products and their relation with porosity evolution, and to reconstruct the fluid flow history prior to and during oil emplacement. On the basis of petrological observations and geochemical analyses (major, minor and trace element composition and oxygen, carbon and strontium isotope composition), a major dolomitization event is recognized postdating subaerial exposure, erosion and karstification. The dolomitization event originated two replacive dolomites (RD1 and RD2) and two dolomite cements (saddle dolomite cement, SDC, and milky-white dolomite cement, MDC) which are partially cogenetic. RD1, RD2 and SDC precipitated at increasing temperatures (over 60ºC and below 110ºC), probably from meteoric water mixed with marine water. The last dolomite type (milky-white dolomite cement) precipitated with increasing burial conditions and by arrival of hydrothermal fluids during the Miocene. The post-dolomitization sequence comprises precipitation of calcite cement and partial calcitization of all previous dolomites. The oxygen, carbon and strontium isotope compositions suggest that this calcite cementation occurred from meteoric waters mixed with Burdigalian - Langhian marine waters trapped in the sediments and expelled by compaction in the moderate to deep burial realm. Normal faults were the conduits for upward migration of these fluids as well as for later oil expulsion from the Burdigalian - Langhian source rocks. Late corrosion associated with organic acid-enriched fluids took place prior or simultaneously to oil migration during the Pliocene, enhancing porosity and increasing reservoir quality

Origin of the coloured karst fills in the neogene extensional system of ne iberia (Spain)

Karst fills from the onshore Penedès Basin and offshore València Trough display red, pink, orange and ochre colours. Their Mössbauer spectra indicate that Fe contained in goethite is the dominant species in reddish-pink fills, whereas Fe contained in dolomite and clays is more dominant in the orange and ochre ones. The lower δ C values and higher Sr/ Sr ratios of the karst fills with respect to their host carbonates can reflect the input of soil-derived CO and an external radiogenic source into the karst system. This geochemical composition, together with the non-carbonate fraction of the fills, consists of authigenic and transported illite, illite-smectite interlayers, as well as kaolinite, chlorite, pyrite, quartz, ilmenite, magnetite, apatite and feldspar, account for a mixed residual-detrital origin of fills. This polygenic origin agrees with that of the terra rossa sediments described worldwide. The different colours of karst fills are attributed to fluctuations in the water table, which control the Eh/pH conditions in the karst system. Thus, reddish colours reflect low water table levels and oxidising episodes, and orange and ochre ones reflect high water table levels and more reducing episodes. The greenish colours of fills could be related to fluctuations in the Fe /Fe ratio

Origin of the coloured karst fills in the neogene extensional system of ne iberia (Spain)

Karst fills from the onshore Penedès Basin and offshore València Trough display red, pink, orange and ochre colours. Their Mössbauer spectra indicate that Fe3+ contained in goethite is the dominant species in reddish-pink fills, whereas Fe2+ contained in dolomite and clays is more dominant in the orange and ochre ones. The lower δ 13C values and higher 87Sr/86Sr ratios of the karst fills with respect to their host carbonates can reflect the input of soil-derived CO2 and an external radiogenic source into the karst system. This geochemical composition, together with the non-carbonate fraction of the fills, consists of authigenic and transported illite, illite-smectite interlayers, as well as kaolinite, chlorite, pyrite, quartz, ilmenite, magnetite, apatite and feldspar, account for a mixed residual-detrital origin of fills. This polygenic origin agrees with that of the terra rossa sediments described worldwide. The different colours of karst fills are attributed to fluctuations in the water table, which control the Eh/pH conditions in the karst system. Thus, reddish colours reflect low water table levels and oxidising episodes, and orange and ochre ones reflect high water table levels and more reducing episodes. The greenish colours of fills could be related to fluctuations in the Fe3+/Fe2+ ratio

Formación y sellado de fracturas en un cuerpo salino del subsuelo: el anticlinal de Súria (Pirineos sudorientales)

Las rocas de sal normalmente se deforman principalmente de forma dúctil e impiden la circulación de fluidos. Sin embargo, los cuerpos salinos a veces se pueden fracturar y presentar permeabilidad. Esta contribución presenta ejemplos de fracturación y sellado en halita en el anticlinal de Súria, un cuerpo salino de los pirineos Sudorientales altamente deformado. El análisis de afloramientos en galerías de la mina de potasa de Cabanasses muestra que hay redes densas de venas formadas por cristales de calcita grandes y limpios que cortan a una roca encajante compuesta principalmente de halita. En este trabajo se ha realizado un análisis estructural de orientaciones de venas, junto con el estudio de láminas delgadas y contenido de bromo (Br) en las venas y sus rocas de caja. Las rocas encajantes de la unidad de halita-silvinita sufrieron recristalización dinámica y presentan una orientación preferente de bordes de grano (SPO), pliegues isoclinales, zonas de cizalla y niveles de despegue. Por otro lado, las rocas encajantes de la unidad de halita inferior, que se encuentra por debajo de la halita-silvinita, son más competentes que estas y sufrieron recristalización y disolución. El contenido en Br de las rocas encajantes se incrementa hacia arriba, reflejando el cierre de la cuenca evaporítica marina y un aumento de la concentración de la salmuera marina por evaporación. La fuerte deformación por presión-disolución, creep de dislocaciones y recristalización produjo disolución de cristales y transferencia de Br de la roca encajante a la salmuera El contenido en Br de las venas es similar al de su roca de caja en la unidad de halita inferior, pero las venas de la unidad de halita-silvinita contienen menos Br que su roca encajante, mostrando que el fluido mineralizante fluyó de abajo hacia arriba. La unidad de potasa, que se sitúa sobre las unidades de halita inferior y halita-silvinita, es más dúctil que estas y por lo tanto no se fracturó, ejerciendo de sello para las salmueras que formaron las venas.</p

Interpretación de los contenidos en elementos minoritarios en la sal de mesa mediante FRX.

La sal de mesa es el único mineral comestible que se consume diariamente. El interés por este producto ha crecido en las últimas décadas en la cultura gastronómica, presentándose como un producto gourmet, muy apreciado en la alta cocina

Podem fer ApS virtual?: creació d’una plataforma de difusió d’activitats de ciències de la terra per a estudiants d’ESO [Informe final PID 2020PID-UB/039]

Projecte PID: 2020PID-UB/039El projecte proposa la creació de diverses activitats virtuals, dinàmiques i vives, allotjades en el servidor de la UB, i que serveixin com a plataforma de llançament per a la incorporació, la difusió i la implementació de noves propostes futures amb un marcat caire innovador. Totes s’emmarquen en l’àmbit de l’educació i divulgació científica dins de les assignatures de Treball de Final de Grau (TFG) i de màster (TFM) que es realitzen a les facultats de Ciències de la Terra i Biologia de la Universitat de Barcelona. Aquesta actuació ha impulsat definitivament la metodologia docent d’Aprenentatge-Servei (ApS) a la Facultat de Ciències de la Terra i en ensenyaments que continguin assignatures relacionades amb les Ciències de la Terra i el Medi Ambient, i han millorat la transferència de coneixements geològics cap a la Societat.S’han generat 3 projectes virtuals d'accés gratuït que inclouran conceptes de ciències de caire transversal i dinamitzador, Aquests projectes han estat dissenyats per l’alumnat del grau de geologia, el grau de ciències ambientals i el màster de formació del professorat de l’especialitat de Biologia i Geologia en el marc dels seus TFG i TFM. Les activitats estan relaciones amb el currículum de Ciències de la Terra, i destinades a l’estudiat d’ESO i Batxillerat. El desenvolupament de les activitats, així, implica també la seva implementació i avaluació en almenys un institut pilot.En definitiva, es vol demostrar que la resposta a la pregunta proposada al títol del projecte “Podem fer ApS virtual?” és clarament sí, tot i les aparents restriccions i contradiccions que sembla implicar el propi concepte ApS amb la metodologia docent virtual

Compartir ideas, la universidad va al instituto. Análisis de la primera edición de un proyecto de aprendizaje servicio transversal a la Universidad de Barcelona

Esta comunicación presenta las principales claves de análisis y evaluación de la 1a edición del proyecto Compartir Ideas. La Universidad va al instituto. Este es un proyecto de aprendizaje servicio transversal que consiste en un ciclo de conferencias-taller impartidas por estudiantes de la UB sobre temes de interés general relacionados con sus estudios. El objetivo es compartir conocimientos y conversar sobre un tema que la universidad trabaja y que será relevante para la formación del alumnado de secundaria.El proyecto cuenta con el apoyo del Vicerectorado de Política Docente y Lingüística de la Universitat de Barcelona

COVID-19 Sequelae and the Host Pro-Inflammatory Response: An Analysis From the OnCovid Registry

Background: Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post–COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae. / Methods: OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided. / Results: Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR = 0.57, 95% CI: 0.36 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found. / Conclusions: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development